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Current Protein & Peptide Science

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ISSN (Print): 1389-2037
ISSN (Online): 1875-5550

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Review Article

Dynamics of Ubiquitination in Differentiation and Dedifferentiation of Pancreatic β-cells: Putative Target for Diabetes

Author(s): Meenal Francis, Smitha Bhaskar, Sreya Vishnuvajhala, Jyothi Prasanna and Anujith Kumar*

Volume 23, Issue 9, 2022

Published on: 12 October, 2022

Page: [602 - 618] Pages: 17

DOI: 10.2174/1389203723666220422092023

Price: $65

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Abstract

Impairment in the function of insulin-producing pancreatic β-cells is a hallmark of both type 1 and 2 diabetes (T1D/T2D). Despite over a century of effort, there is still no precise treatment regimen available for acute diabetes. Enhancing the endogenous β-cells either by protecting them from apoptosis or dedifferentiation is a classic alternative to retaining the β-cell pool. Recent reports have acknowledged the protein homeostasis mediated by the ubiquitin-proteasome system as one of the essential components in maintaining the β-cell pool. Degradation of the targeted substrate by the proteasome is majorly regulated by the ubiquitination status of the targeted protein dictated by E3 ligases and deubiquitinase enzymes. Imbalance in the function of these enzymes results in the malfunction of β-cells and, subsequently, hyperglycemia. Ubiquitination involves the covalent attachment of one or more ubiquitin moieties to the target protein by E3 ubiquitin ligases and deubiquitinases (DUBs) are the enzymes that antagonize the action of E3 ligases. Knowing different E3 ligases and deubiquitinases in the process of differentiation and dedifferentiation of β-cells probably paves the way for designing novel modulators that enhance either the differentiation or abate the dedifferentiation process. In this review, we will discuss the importance of the balanced ubiquitination process, an understanding of which would facilitate the restraining of β-cells from exhaustion.

Keywords: Diabetes, intracellular protein degradation, proteasome, pancreas, dedifferentiation, differentiation.

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[1]
Mellitus, D. Diagnosis and classification of diabetes mellitus. Diabetes Care, 2005, 28(S37)(Suppl. 1), S37-S42.
[PMID: 15618111]
[2]
Cerf, M.E. Beta cell dysfunction and insulin resistance. Front. Endocrinol. (Lausanne), 2013, 4, 37.
[http://dx.doi.org/10.3389/fendo.2013.00037] [PMID: 23542897]
[3]
Christensen, A.A.; Gannon, M. The beta cell in type 2 diabetes. Curr. Diab. Rep., 2019, 19(9), 81.
[http://dx.doi.org/10.1007/s11892-019-1196-4] [PMID: 31399863]
[4]
Tuomi, T. Type 1 and type 2 diabetes: what do they have in common? Diabetes, 2005, 54(Suppl. 2), S40-S45.
[http://dx.doi.org/10.2337/diabetes.54.suppl_2.S40] [PMID: 16306339]
[5]
Kharroubi, A.T.; Darwish, H.M. Diabetes mellitus: The epidemic of the century. World J. Diabetes, 2015, 6(6), 850-867.
[http://dx.doi.org/10.4239/wjd.v6.i6.850] [PMID: 26131326]
[6]
Brereton, M.F.; Rohm, M.; Ashcroft, F.M. β-Cell dysfunction in diabetes: A crisis of identity? Diabetes Obes. Metab., 2016, 18(Suppl. 1), 102-109.
[http://dx.doi.org/10.1111/dom.12732] [PMID: 27615138]
[7]
Moreno-Amador, J.L.; Téllez, N.; Marin, S.; Aloy-Reverté, C.; Semino, C.; Nacher, M.; Montanya, E. Epithelial to mesenchymal transition in human endocrine islet cells. PLoS One, 2018, 13(1), e0191104.
[http://dx.doi.org/10.1371/journal.pone.0191104] [PMID: 29360826]
[8]
Cole, L.; Anderson, M.; Antin, P.B.; Limesand, S.W. One process for pancreatic β-cell coalescence into islets involves an epithelial-mesenchymal transition. J. Endocrinol., 2009, 203(1), 19-31.
[http://dx.doi.org/10.1677/JOE-09-0072] [PMID: 19608613]
[9]
Talchai, C.; Xuan, S.; Lin, H.V.; Sussel, L.; Accili, D. Pancreatic β cell dedifferentiation as a mechanism of diabetic β cell failure. Cell, 2012, 150(6), 1223-1234.
[http://dx.doi.org/10.1016/j.cell.2012.07.029] [PMID: 22980982]
[10]
Moin, A.S.M.; Butler, A.E. Alterations in beta cell identity in type 1 and type 2 diabetes. Curr. Diab. Rep., 2019, 19(9), 83.
[http://dx.doi.org/10.1007/s11892-019-1194-6] [PMID: 31401713]
[11]
Cerf, M.E. Transcription factors regulating β-cell function. Eur. J. Endocrinol., 2006, 155(5), 671-679.
[http://dx.doi.org/10.1530/eje.1.02277] [PMID: 17062882]
[12]
Fujitani, Y. Transcriptional regulation of pancreas development and β-cell function (Review). Endocr. J., 2017, 64(5), 477-486.
[http://dx.doi.org/10.1507/endocrj.EJ17-0098] [PMID: 28420858]
[13]
López-Avalos, M.D.; Duvivier-Kali, V.F.; Xu, G.; Bonner-Weir, S.; Sharma, A.; Weir, G.C. Evidence for a role of the ubiquitin-proteasome pathway in pancreatic islets. Diabetes, 2006, 55(5), 1223-1231.
[http://dx.doi.org/10.2337/db05-0450] [PMID: 16644676]
[14]
Petroski, M.D. The ubiquitin system, disease, and drug discovery. BMC Biochem., 2008, 9(1)(Suppl. 1), S7.
[http://dx.doi.org/10.1186/1471-2091-9-S1-S7] [PMID: 19007437]
[15]
Hartley, T.; Brumell, J.; Volchuk, A. Emerging roles for the ubiquitin-proteasome system and autophagy in pancreatic β-cells. Am. J. Physiol. Endocrinol. Metab., 2009, 296(1), E1-E10.
[http://dx.doi.org/10.1152/ajpendo.90538.2008] [PMID: 18812463]
[16]
Callis, J. The ubiquitination machinery of the ubiquitin system. Arabidopsis Book, 2014, 12, e0174.
[http://dx.doi.org/10.1199/tab.0174] [PMID: 25320573]
[17]
Varshavsky, A. The ubiquitin system, autophagy, and regulated protein degradation. Annu. Rev. Biochem., 2017, 86, 123-128.
[http://dx.doi.org/10.1146/annurev-biochem-061516-044859] [PMID: 28654326]
[18]
Nandi, D.; Tahiliani, P.; Kumar, A.; Chandu, D. The ubiquitin-proteasome system. J. Biosci., 2006, 31(1), 137-155.
[http://dx.doi.org/10.1007/BF02705243] [PMID: 16595883]
[19]
Lee, C.S.; Kim, S.; Hwang, G.; Song, J. Deubiquitinases:] Modulators of different types of regulated cell death. Int. J. Mol. Sci., 2021, 22(9), 4352.
[http://dx.doi.org/10.3390/ijms22094352] [PMID: 33919439]
[20]
Celebi, G.; Kesim, H.; Ozer, E.; Kutlu, O. The effect of] dysfunctional ubiquitin enzymes in the pathogenesis of most common diseases. Int. J. Mol. Sci., 2020, 21(17), 6335.
[http://dx.doi.org/10.3390/ijms21176335] [PMID: 32882786]
[21]
Jaisson, S.; Gillery, P. Impaired proteostasis: Role in the pathogenesis of diabetes mellitus. Diabetologia, 2014, 57(8), 1517-1527.
[http://dx.doi.org/10.1007/s00125-014-3257-1] [PMID: 24816368]
[22]
Aghdam, S.Y.; Gurel, Z.; Ghaffarieh, A.; Sorenson, C.M.; Sheibani, N. High glucose and diabetes modulate cellular proteasome function: Implications in the pathogenesis of diabetes complications. Biochem. Biophys. Res. Commun., 2013, 432(2), 339-344.
[http://dx.doi.org/10.1016/j.bbrc.2013.01.101] [PMID: 23391566]
[23]
Liu, H.; Yu, S.; Xu, W.; Xu, J. Enhancement of 26S proteasome functionality connects oxidative stress and vascular endothelial inflammatory response in diabetes mellitus. Arterioscler. Thromb. Vasc. Biol., 2012, 32(9), 2131-2140.
[http://dx.doi.org/10.1161/ATVBAHA.112.253385] [PMID: 22772755]
[24]
Xu, J.; Wang, S.; Zhang, M.; Wang, Q.; Asfa, S.; Zou, M.H. Tyrosine nitration of PA700 links proteasome activation to endothelial dysfunction in mouse models with cardiovascular risk factors. PLoS One, 2012, 7(1), e29649.
[http://dx.doi.org/10.1371/journal.pone.0029649] [PMID: 22272240]
[25]
Solnica-Krezel, L. Conserved patterns of cell movements during vertebrate gastrulation. Curr. Biol., 2005, 15(6), R213-R228.
[http://dx.doi.org/10.1016/j.cub.2005.03.016] [PMID: 15797016]
[26]
Gittes, G.K. Developmental biology of the pancreas: A comprehensive review. Dev. Biol., 2009, 326(1), 4-35.
[http://dx.doi.org/10.1016/j.ydbio.2008.10.024] [PMID: 19013144]
[27]
Wang, J.; Laurie, G.W. Organogenesis of the exocrine gland. Dev. Biol., 2004, 273(1), 1-22.
[http://dx.doi.org/10.1016/j.ydbio.2004.05.025] [PMID: 15302594]
[28]
Bastidas-Ponce, A.; Scheibner, K.; Lickert, H.; Bakhti, M. Cellular and molecular mechanisms coordinating pancreas development. Development, 2017, 144(16), 2873-2888.
[http://dx.doi.org/10.1242/dev.140756] [PMID: 28811309]
[29]
Hebrok, M. Hedgehog signaling in pancreas development. Mech. Dev., 2003, 120(1), 45-57.
[http://dx.doi.org/10.1016/S0925-4773(02)00331-3] [PMID: 12490295]
[30]
Gradwohl, G.; Dierich, A.; LeMeur, M.; Guillemot, F. neurogenin3 is required for the development of the four endocrine cell lineages of the pancreas. Proc. Natl. Acad. Sci. USA, 2000, 97(4), 1607-1611.
[http://dx.doi.org/10.1073/pnas.97.4.1607] [PMID: 10677506]
[31]
Gouzi, M.; Kim, Y.H.; Katsumoto, K.; Johansson, K.; Grapin-Botton, A. Neurogenin3 initiates stepwise delamination of differentiating endocrine cells during pancreas development. Dev. Dyn., 2011, 240(3), 589-604.
[http://dx.doi.org/10.1002/dvdy.22544] [PMID: 21287656]
[32]
Rukstalis, J.M.; Habener, J.F. Snail2, a mediator of epithelial-mesenchymal transitions, expressed in progenitor cells of the developing endocrine pancreas. Gene Expr. Patterns, 2007, 7(4), 471-479.
[http://dx.doi.org/10.1016/j.modgep.2006.11.001] [PMID: 17185046]
[33]
Zhang, J.; Tian, X.J.; Xing, J. Signal transduction pathways of EMT induced by TGF-β, SHH, and WNT and their crosstalks. J. Clin. Med., 2016, 5(4), 41.
[http://dx.doi.org/10.3390/jcm5040041] [PMID: 27043642]
[34]
Petri, A.; Ahnfelt-Rønne, J.; Frederiksen, K.S.; Edwards, D.G.; Madsen, D.; Serup, P.; Fleckner, J.; Heller, R.S. The effect of neurogenin3 deficiency on pancreatic gene expression in embryonic mice. J. Mol. Endocrinol., 2006, 37(2), 301-316.
[http://dx.doi.org/10.1677/jme.1.02096] [PMID: 17032746]
[35]
Wang, S.; Yan, J.; Anderson, D.A.; Xu, Y.; Kanal, M.C.; Cao, Z.; Wright, C.V.; Gu, G. Neurog3 gene dosage regulates allocation of endocrine and exocrine cell fates in the developing mouse pancreas. Dev. Biol., 2010, 339(1), 26-37.
[http://dx.doi.org/10.1016/j.ydbio.2009.12.009] [PMID: 20025861]
[36]
Courtney, M.; Rabe, T.; Collombat, P.; Mansouri, A. Pax4 and Arx represent crucial regulators of the development of the endocrine pancreas. New J. Sci., 2014, 2014, 6.
[http://dx.doi.org/10.1155/2014/981569]
[37]
Zhu, Y.; Liu, Q.; Zhou, Z.; Ikeda, Y. PDX1, Neurogenin-3, and MAFA: critical transcription regulators for beta cell development and regeneration. Stem Cell Res. Ther., 2017, 8(1), 240.
[http://dx.doi.org/10.1186/s13287-017-0694-z] [PMID: 29096722]
[38]
Liu, Z.; Habener, J.F. Alpha cells beget beta cells. Cell, 2009, 138(3), 424-426.
[http://dx.doi.org/10.1016/j.cell.2009.07.022] [PMID: 19665963]
[39]
Zhang, Y.; Fava, G.E.; Wang, H.; Mauvais-Jarvis, F.; Fonseca, V.A.; Wu, H. PAX4 gene transfer induces α-to-β cell phenotypic conversion and confers therapeutic benefits for diabetes treatment. Mol. Ther., 2016, 24(2), 251-260.
[http://dx.doi.org/10.1038/mt.2015.181] [PMID: 26435408]
[40]
Chakravarthy, H.; Gu, X.; Enge, M.; Dai, X.; Wang, Y.; Damond, N.; Downie, C.; Liu, K.; Wang, J.; Xing, Y.; Chera, S.; Thorel, F.; Quake, S.; Oberholzer, J.; MacDonald, P.E.; Herrera, P.L.; Kim, S.K. Converting adult pancreatic islet α cells into β cells by targeting both Dnmt1 and Arx. Cell Metab., 2017, 25(3), 622-634.
[http://dx.doi.org/10.1016/j.cmet.2017.01.009] [PMID: 28215845]
[41]
Elghazi, L.; Bernal-Mizrachi, E. Akt and PTEN: β-cell mass and pancreas plasticity. Trends Endocrinol. Metab., 2009, 20(5), 243-251.
[http://dx.doi.org/10.1016/j.tem.2009.03.002] [PMID: 19541499]
[42]
Dhawan, S.; Georgia, S.; Tschen, S.I.; Fan, G.; Bhushan, A. Pancreatic β cell identity is maintained by DNA methylation-mediated repression of Arx. Dev. Cell, 2011, 20(4), 419-429.
[http://dx.doi.org/10.1016/j.devcel.2011.03.012] [PMID: 21497756]
[43]
Cieślar-Pobuda, A.; Knoflach, V.; Ringh, M.V.; Stark, J.; Likus, W.; Siemianowicz, K.; Ghavami, S.; Hudecki, A.; Green, J.L.; Łos, M.J. Transdifferentiation and reprogramming: Overview of the processes, their similarities and differences. Biochim. Biophys. Acta Mol. Cell Res., 2017, 1864(7), 1359-1369.
[http://dx.doi.org/10.1016/j.bbamcr.2017.04.017] [PMID: 28460880]
[44]
Pesaresi, M.; Sebastian-Perez, R.; Cosma, M.P. Dedifferentiation, transdifferentiation and cell fusion: in vivo reprogramming strategies for regenerative medicine. FEBS J., 2019, 286(6), 1074-1093.
[http://dx.doi.org/10.1111/febs.14633] [PMID: 30103260]
[45]
Lemaire, K.; Thorrez, L.; Schuit, F. Disallowed and allowed gene expression: two faces of mature islet beta cells. Annu. Rev. Nutr., 2016, 36, 45-71.
[http://dx.doi.org/10.1146/annurev-nutr-071715-050808] [PMID: 27146011]
[46]
Sun, T.; Han, X. Death versus dedifferentiation: The molecular bases of beta cell mass reduction in type 2 diabetes. Semin. Cell Dev. Biol., 2020, 103, 76-82.
[http://dx.doi.org/10.1016/j.semcdb.2019.12.002] [PMID: 31831356]
[47]
Weir, G.C.; Aguayo-Mazzucato, C.; Bonner-Weir, S. β-cell dedifferentiation in diabetes is important, but what is it? Islets, 2013, 5(5), 233-237.
[http://dx.doi.org/10.4161/isl.27494] [PMID: 24356710]
[48]
Amo-Shiinoki, K.; Tanabe, K.; Hoshii, Y.; Matsui, H.; Harano, R.; Fukuda, T.; Takeuchi, T.; Bouchi, R.; Takagi, T.; Hatanaka, M.; Takeda, K.; Okuya, S.; Nishimura, W.; Kudo, A.; Tanaka, S.; Tanabe, M.; Akashi, T.; Yamada, T.; Ogawa, Y.; Ikeda, E.; Nagano, H.; Tanizawa, Y. Islet cell dedifferentiation is a pathologic mechanism of long-standing progression of type 2 diabetes. JCI Insight, 2021, 6(1), e143791.
[http://dx.doi.org/10.1172/jci.insight.143791] [PMID: 33427207]
[49]
Kaiser, N.; Leibowitz, G.; Nesher, R. Glucotoxicity and beta-cell failure in type 2 diabetes mellitus. J. Pediatr. Endocrinol. Metab., 2003, 16(1), 5-22.
[http://dx.doi.org/10.1515/JPEM.2003.16.1.5] [PMID: 12585335]
[50]
Guo, S.; Dai, C.; Guo, M.; Taylor, B.; Harmon, J.S.; Sander, M.; Robertson, R.P.; Powers, A.C.; Stein, R. Inactivation of specific β cell transcription factors in type 2 diabetes. J. Clin. Invest., 2013, 123(8), 3305-3316.
[http://dx.doi.org/10.1172/JCI65390] [PMID: 23863625]
[51]
Kaneto, H.; Matsuoka, T.A. Down-regulation of pancreatic transcription factors and incretin receptors in type 2 diabetes. World J. Diabetes, 2013, 4(6), 263-269.
[http://dx.doi.org/10.4239/wjd.v4.i6.263] [PMID: 24379916]
[52]
Md Moin, A.S.; Dhawan, S.; Shieh, C.; Butler, P.C.; Cory, M.; Butler, A.E. Increased hormone-negative endocrine cells in the pancreas in type 1 diabetes. J. Clin. Endocrinol. Metab., 2016, 101(9), 3487-3496.
[http://dx.doi.org/10.1210/jc.2016-1350] [PMID: 27300574]
[53]
Fonseca, S.G.; Gromada, J.; Urano, F. Endoplasmic reticulum stress and pancreatic β-cell death. Trends Endocrinol. Metab., 2011, 22(7), 266-274.
[http://dx.doi.org/10.1016/j.tem.2011.02.008] [PMID: 21458293]
[54]
Back, S.H.; Kaufman, R.J. Endoplasmic reticulum stress and type 2 diabetes. Annu. Rev. Biochem., 2012, 81, 767-793.
[http://dx.doi.org/10.1146/annurev-biochem-072909-095555] [PMID: 22443930]
[55]
Hu, Y.; Gao, Y.; Zhang, M.; Deng, K.Y.; Singh, R.; Tian, Q.; Gong, Y.; Pan, Z.; Liu, Q.; Boisclair, Y.R.; Long, Q. Endoplasmic reticulum–associated degradation (ERAD) has a critical role in supporting glucose-stimulated insulin secretion in pancreatic β-cells. Diabetes, 2019, 68(4), 733-746.
[http://dx.doi.org/10.2337/db18-0624] [PMID: 30626610]
[56]
Costes, S.; Huang, C.J.; Gurlo, T.; Daval, M.; Matveyenko, A.V.; Rizza, R.A.; Butler, A.E.; Butler, P.C. β-cell dysfunctional ERAD/ubiquitin/proteasome system in type 2 diabetes mediated by islet amyloid polypeptide-induced UCH-L1 deficiency. Diabetes, 2011, 60(1), 227-238.
[http://dx.doi.org/10.2337/db10-0522] [PMID: 20980462]
[57]
Xiao, X.; Fischbach, S.; Zhang, T.; Chen, C.; Sheng, Q.; Zimmerman, R.; Patnaik, S.; Fusco, J.; Ming, Y.; Guo, P.; Shiota, C.; Prasadan, K.; Gangopadhyay, N.; Husain, S.Z.; Dong, H.; Gittes, G.K. Smad3/stat3 signaling mediates β-cell epithelial-mesenchymal transition in chronic pancreatitis–related diabetes. Diabetes, 2017, 66(10), 2646-2658.
[http://dx.doi.org/10.2337/db17-0537] [PMID: 28775125]
[58]
Liu, N.; Cai, X.; Liu, T.; Zou, J.; Wang, L.; Wang, G.; Liu, Y.; Ding, X.; Zhang, B.; Sun, P.; Liang, R.; Wang, S. Hypoxia-inducible factor-1α mediates the expression of mature β cell-disallowed genes in hypoxia-induced β cell dedifferentiation. Biochem. Biophys. Res. Commun., 2020, 523(2), 382-388.
[http://dx.doi.org/10.1016/j.bbrc.2019.12.063] [PMID: 31866014]
[59]
Ježek, P.; Jabůrek, M.; Plecitá-Hlavatá, L. Contribution of oxidative stress and impaired biogenesis of pancreatic β-cells to type 2 diabetes. Antioxid. Redox Signal., 2019, 31(10), 722-751.
[http://dx.doi.org/10.1089/ars.2018.7656] [PMID: 30450940]
[60]
Kaneto, H.; Xu, G.; Fujii, N.; Kim, S.; Bonner-Weir, S.; Weir, G.C. Involvement of c-Jun N-terminal kinase in oxidative stress-mediated suppression of insulin gene expression. J. Biol. Chem., 2002, 277(33), 30010-30018.
[http://dx.doi.org/10.1074/jbc.M202066200] [PMID: 12011047]
[61]
Kaneto, H.; Sharma, A.; Suzuma, K.; Laybutt, D.R.; Xu, G.; Bonner-Weir, S.; Weir, G.C. Induction of c-Myc expression suppresses insulin gene transcription by inhibiting NeuroD/BETA2-mediated transcriptional activation. J. Biol. Chem., 2002, 277(15), 12998-13006.
[http://dx.doi.org/10.1074/jbc.M111148200] [PMID: 11799123]
[62]
Jonas, J.C.; Laybutt, D.R.; Steil, G.M.; Trivedi, N.; Pertusa, J.G.; Van de Casteele, M.; Weir, G.C.; Henquin, J.C. High glucose stimulates early response gene c-Myc expression in rat pancreatic beta cells. J. Biol. Chem., 2001, 276(38), 35375-35381.
[http://dx.doi.org/10.1074/jbc.M105020200] [PMID: 11457846]
[63]
Kitamura, Y.I.; Kitamura, T.; Kruse, J.P.; Raum, J.C.; Stein, R.; Gu, W.; Accili, D. FoxO1 protects against pancreatic β cell failure through NeuroD and MafA induction. Cell Metab., 2005, 2(3), 153-163.
[http://dx.doi.org/10.1016/j.cmet.2005.08.004] [PMID: 16154098]
[64]
Zhang, T.; Kim, D.H.; Xiao, X.; Lee, S.; Gong, Z.; Muzumdar, R.; Calabuig-Navarro, V.; Yamauchi, J.; Harashima, H.; Wang, R.; Bottino, R.; Alvarez-Perez, J.C.; Garcia-Ocaña, A.; Gittes, G.; Dong, H.H. FoxO1 plays an important role in regulating β-cell compensation for insulin resistance in male mice. Endocrinology, 2016, 157(3), 1055-1070.
[http://dx.doi.org/10.1210/en.2015-1852] [PMID: 26727107]
[65]
Wolf, G.; Wenzel, U.; Burns, K.D.; Harris, R.C.; Stahl, R.A.; Thaiss, F. Angiotensin II activates nuclear transcription factor-kappaB through AT1 and AT2 receptors. Kidney Int., 2002, 61(6), 1986-1995.
[http://dx.doi.org/10.1046/j.1523-1755.2002.00365.x] [PMID: 12028439]
[66]
Chen, H.; Zhou, W.; Ruan, Y. Reversal of angiotensin ll-induced β-cell dedifferentiation via inhibition of NF-κb signaling. Mol. Med., 2018, 24(1), 1-2.
[http://dx.doi.org/10.1186/s10020-018-0044-3] [PMID: 30134794]
[67]
Salinno, C.; Büttner, M.; Cota, P.; Tritschler, S.; Tarquis-Medina, M.; Bastidas-Ponce, A.; Scheibner, K.; Burtscher, I.; Böttcher, A.; Theis, F.J.; Bakhti, M.; Lickert, H. CD81 marks immature and dedifferentiated pancreatic β-cells. Mol. Metab., 2021, 49, 101188.
[http://dx.doi.org/10.1016/j.molmet.2021.101188] [PMID: 33582383]
[68]
Fan, J.; Du, W.; Kim-Muller, J.Y.; Son, J.; Kuo, T.; Larrea, D.; Garcia, C.; Kitamoto, T.; Kraakman, M.J.; Owusu-Ansah, E.; Cirulli, V.; Accili, D. Cyb5r3 links FoxO1-dependent mitochondrial dysfunction with β-cell failure. Mol. Metab., 2020, 34, 97-111.
[http://dx.doi.org/10.1016/j.molmet.2019.12.008] [PMID: 32180563]
[69]
Cinti, F.; Mezza, T.; Severi, I.; Suleiman, M.; Cefalo, C.M.A.; Sorice, G.P.; Moffa, S.; Impronta, F.; Quero, G.; Alfieri, S.; Mari, A.; Pontecorvi, A.; Marselli, L.; Cinti, S.; Marchetti, P.; Giaccari, A. Noradrenergic fibers are associated with beta-cell dedifferentiation and impaired beta-cell function in humans. Metabolism, 2021, 114, 154414.
[http://dx.doi.org/10.1016/j.metabol.2020.154414] [PMID: 33129839]
[70]
Lee, H.; Lee, Y.S.; Harenda, Q.; Pietrzak, S.; Oktay, H.Z.; Schreiber, S.; Liao, Y.; Sonthalia, S.; Ciecko, A.E.; Chen, Y.G.; Keles, S.; Sridharan, R.; Engin, F. Beta cell dedifferentiation induced by IRE1α deletion prevents type 1 diabetes. Cell Metab., 2020, 31(4), 822-836.
[http://dx.doi.org/10.1016/j.cmet.2020.03.002] [PMID: 32220307]
[71]
Puri, S.; Folias, A.E.; Hebrok, M. Plasticity and dedifferentiation within the pancreas: development, homeostasis, and disease. Cell Stem Cell, 2015, 16(1), 18-31.
[http://dx.doi.org/10.1016/j.stem.2014.11.001] [PMID: 25465113]
[72]
Russ, H.A.; Sintov, E.; Anker-Kitai, L.; Friedman, O.; Lenz, A.; Toren, G.; Farhy, C.; Pasmanik-Chor, M.; Oron-Karni, V.; Ravassard, P.; Efrat, S. Insulin-producing cells generated from dedifferentiated human pancreatic beta cells expanded in vitro. PLoS One, 2011, 6(9), e25566.
[http://dx.doi.org/10.1371/journal.pone.0025566] [PMID: 21984932]
[73]
Wang, H.; Unternaehrer, J.J. Epithelial-mesenchymal transition and cancer stem cells: at the crossroads of differentiation and] dedifferentiation. Dev. Dyn., 2019, 248(1), 10-20.
[http://dx.doi.org/10.1002/dvdy.24678] [PMID: 30303578]
[74]
Khunti, K.; Alsifri, S.; Aronson, R.; Cigrovski Berković, M.; Enters-Weijnen, C.; Forsén, T.; Galstyan, G.; Geelhoed-Duijvestijn, P.; Goldfracht, M.; Gydesen, H.; Kapur, R.; Lalic, N.; Ludvik, B.; Moberg, E.; Pedersen-Bjergaard, U.; Ramachandran, A. Rates and predictors of hypoglycaemia in 27 585 people from 24 countries with insulin-treated type 1 and type 2 diabetes: The global HAT study. Diabetes Obes. Metab., 2016, 18(9), 907-915.
[http://dx.doi.org/10.1111/dom.12689] [PMID: 27161418]
[75]
Mak, T.C.; von Ohlen, Y.; Wang, Y.F. β-cell dedifferentiation is associated with epithelial-mesenchymal transition triggered by miR-7-mediated repression of mSwi/Snf complex. bioRxiv, 2019, 789461.
[http://dx.doi.org/10.1101/789461]
[76]
Coll-Martínez, B.; Crosas, B. How the 26S proteasome degrades ubiquitinated proteins in the cell. Biomolecules, 2019, 9(9), 395.
[http://dx.doi.org/10.3390/biom9090395] [PMID: 31443414]
[77]
Herrmann, J.; Lerman, L.O.; Lerman, A. Ubiquitin and ubiquitin-like proteins in protein regulation. Circ. Res., 2007, 100(9), 1276-1291.
[http://dx.doi.org/10.1161/01.RES.0000264500.11888.f0] [PMID: 17495234]
[78]
Komander, D.; Rape, M. The ubiquitin code. Annu. Rev. Biochem., 2012, 81, 203-229.
[http://dx.doi.org/10.1146/annurev-biochem-060310-170328] [PMID: 22524316]
[79]
Yau, R.; Rape, M. The increasing complexity of the ubiquitin code. Nat. Cell Biol., 2016, 18(6), 579-586.
[http://dx.doi.org/10.1038/ncb3358] [PMID: 27230526]
[80]
Grice, G.L.; Nathan, J.A. The recognition of ubiquitinated proteins by the proteasome. Cell. Mol. Life Sci., 2016, 73(18), 3497-3506.
[http://dx.doi.org/10.1007/s00018-016-2255-5] [PMID: 27137187]
[81]
Pickart, C.M.; Eddins, M.J. Ubiquitin: Structures, functions, mechanisms. Biochim. Biophys. Acta, 2004, 1695(1-3), 55-72.
[http://dx.doi.org/10.1016/j.bbamcr.2004.09.019] [PMID: 15571809]
[82]
Bianchi, M.; Giacomini, E.; Crinelli, R.; Radici, L.; Carloni, E.; Magnani, M. Dynamic transcription of ubiquitin genes under basal and stressful conditions and new insights into the multiple UBC transcript variants. Gene, 2015, 573(1), 100-109.
[http://dx.doi.org/10.1016/j.gene.2015.07.030] [PMID: 26172870]
[83]
Sadowski, M.; Sarcevic, B. Mechanisms of mono- and poly-ubiquitination: Ubiquitination specificity depends on compatibility between the E2 catalytic core and amino acid residues proximal to the lysine. Cell Div., 2010, 5(1), 19.
[http://dx.doi.org/10.1186/1747-1028-5-19] [PMID: 20704751]
[84]
Jura, N.; Scotto-Lavino, E.; Sobczyk, A.; Bar-Sagi, D. Differential modification of Ras proteins by ubiquitination. Mol. Cell, 2006, 21(5), 679-687.
[http://dx.doi.org/10.1016/j.molcel.2006.02.011] [PMID: 16507365]
[85]
Schrader, E.K.; Harstad, K.G.; Matouschek, A. Targeting proteins for degradation. Nat. Chem. Biol., 2009, 5(11), 815-822.
[http://dx.doi.org/10.1038/nchembio.250] [PMID: 19841631]
[86]
Erpapazoglou, Z.; Walker, O.; Haguenauer-Tsapis, R. Versatile roles of k63-linked ubiquitin chains in trafficking. Cells, 2014, 3(4), 1027-1088.
[http://dx.doi.org/10.3390/cells3041027] [PMID: 25396681]
[87]
Meyer, H.J.; Rape, M. Enhanced protein degradation by branched ubiquitin chains. Cell, 2014, 157(4), 910-921.
[http://dx.doi.org/10.1016/j.cell.2014.03.037] [PMID: 24813613]
[88]
Ordureau, A.; Münch, C.; Harper, J.W. Quantifying ubiquitin signaling. Mol. Cell, 2015, 58(4), 660-676.
[http://dx.doi.org/10.1016/j.molcel.2015.02.020] [PMID: 26000850]
[89]
Takiuchi, T.; Nakagawa, T.; Tamiya, H.; Fujita, H.; Sasaki, Y.; Saeki, Y.; Takeda, H.; Sawasaki, T.; Buchberger, A.; Kimura, T.; Iwai, K. Suppression of LUBAC-mediated linear ubiquitination by a specific interaction between LUBAC and the deubiquitinases CYLD and OTULIN. Genes Cells, 2014, 19(3), 254-272.
[http://dx.doi.org/10.1111/gtc.12128] [PMID: 24461064]
[90]
Pickart, C.M. Back to the future with ubiquitin. Cell, 2004, 116(2), 181-190.
[http://dx.doi.org/10.1016/S0092-8674(03)01074-2] [PMID: 14744430]
[91]
Metzger, M.B.; Hristova, V.A.; Weissman, A.M. HECT and RING finger families of E3 ubiquitin ligases at a glance. J. Cell Sci., 2012, 125(Pt 3), 531-537.
[http://dx.doi.org/10.1242/jcs.091777] [PMID: 22389392]
[92]
George, A.J.; Hoffiz, Y.C.; Charles, A.J.; Zhu, Y.; Mabb, A.M. A comprehensive atlas of E3 ubiquitin ligase mutations in neurological disorders. Front. Genet., 2018, 9, 29.
[http://dx.doi.org/10.3389/fgene.2018.00029] [PMID: 29491882]
[93]
Kishino, T.; Lalande, M.; Wagstaff, J. UBE3A/E6-AP mutations cause Angelman syndrome. Nat. Genet., 1997, 15(1), 70-73.
[http://dx.doi.org/10.1038/ng0197-70] [PMID: 8988171]
[94]
Metzger, M.B.; Pruneda, J.N.; Klevit, R.E.; Weissman, A.M. RING-type E3 ligases: master manipulators of E2 ubiquitin-conjugating enzymes and ubiquitination. Biochim. Biophys. Acta, 2014, 1843(1), 47-60.
[http://dx.doi.org/10.1016/j.bbamcr.2013.05.026] [PMID: 23747565]
[95]
Liu, L.; Wong, C.C.; Gong, B.; Yu, J. Functional significance and therapeutic implication of ring-type E3 ligases in colorectal cancer. Oncogene, 2018, 37(2), 148-159.
[http://dx.doi.org/10.1038/onc.2017.313] [PMID: 28925398]
[96]
Chasapis, C.T.; Loutsidou, A.K.; Orkoula, M.G.; Spyroulias, G.A. Zinc binding properties of engineered RING finger domain of Arkadia E3 ubiquitin ligase. Bioinorg. Chem. Appl., 2010, 2010, 323152.
[http://dx.doi.org/10.1155/2010/323152] [PMID: 20689703]
[97]
Lorick, K.L.; Jensen, J.P.; Fang, S.; Ong, A.M.; Hatakeyama, S.; Weissman, A.M. RING fingers mediate ubiquitin-conjugating enzyme (E2)-dependent ubiquitination. Proc. Natl. Acad. Sci. USA, 1999, 96(20), 11364-11369.
[http://dx.doi.org/10.1073/pnas.96.20.11364] [PMID: 10500182]
[98]
Branigan, E.; Carlos Penedo, J.; Hay, R.T. Ubiquitin transfer by a RING E3 ligase occurs from a closed E2~ubiquitin conformation. Nat. Commun., 2020, 11(1), 2846.
[http://dx.doi.org/10.1038/s41467-020-16666-y] [PMID: 32503993]
[99]
Dove, K.K.; Stieglitz, B.; Duncan, E.D.; Rittinger, K.; Klevit, R.E. Molecular insights into RBR E3 ligase ubiquitin transfer mechanisms. EMBO Rep., 2016, 17(8), 1221-1235.
[http://dx.doi.org/10.15252/embr.201642641] [PMID: 27312108]
[100]
Spratt, D.E.; Walden, H.; Shaw, G.S. RBR E3 ubiquitin ligases: New structures, new insights, new questions. Biochem. J., 2014, 458(3), 421-437.
[http://dx.doi.org/10.1042/BJ20140006] [PMID: 24576094]
[101]
He, M.; Zhou, Z.; Shah, A.A.; Zou, H.; Tao, J.; Chen, Q.; Wan, Y. The emerging role of deubiquitinating enzymes in genomic integrity, diseases, and therapeutics. Cell Biosci., 2016, 6(1), 62.
[http://dx.doi.org/10.1186/s13578-016-0127-1] [PMID: 28031783]
[102]
Haq, S.; Ramakrishna, S. Deubiquitylation of deubiquitylases. Open Biol., 2017, 7(6), 170016.
[http://dx.doi.org/10.1098/rsob.170016] [PMID: 28659380]
[103]
Reyes-Turcu, F.E.; Wilkinson, K.D. Polyubiquitin binding and disassembly by deubiquitinating enzymes. Chem. Rev., 2009, 109(4), 1495-1508.
[http://dx.doi.org/10.1021/cr800470j] [PMID: 19243136]
[104]
Ostapenko, D.; Burton, J.L.; Solomon, M.J. The Ubp15 deubiquitinase promotes timely entry into S phase in Saccharomyces cerevisiae. Mol. Biol. Cell, 2015, 26(12), 2205-2216.
[http://dx.doi.org/10.1091/mbc.E14-09-1400] [PMID: 25877870]
[105]
Nijman, S.M.; Luna-Vargas, M.P.; Velds, A.; Brummelkamp, T.R.; Dirac, A.M.; Sixma, T.K.; Bernards, R. A genomic and functional inventory of deubiquitinating enzymes. Cell, 2005, 123(5), 773-786.
[http://dx.doi.org/10.1016/j.cell.2005.11.007] [PMID: 16325574]
[106]
Wolberger, C. Mechanisms for regulating deubiquitinating enzymes. Protein Sci., 2014, 23(4), 344-353.
[http://dx.doi.org/10.1002/pro.2415] [PMID: 24403057]
[107]
Amerik, A.Y.; Hochstrasser, M. Mechanism and function of deubiquitinating enzymes. Biochim. Biophys. Acta, 2004, 1695(1-3), 189-207.
[http://dx.doi.org/10.1016/j.bbamcr.2004.10.003] [PMID: 15571815]
[108]
Sun, J.; Shi, X.; Mamun, M.A.A.; Gao, Y. The role of deubiquitinating enzymes in gastric cancer. Oncol. Lett., 2020, 19(1), 30-44.
[PMID: 31897112]
[109]
Ovaa, H.; Kessler, B.M.; Rolén, U.; Galardy, P.J.; Ploegh, H.L.; Masucci, M.G. Activity-based ubiquitin-specific protease (USP) profiling of virus-infected and malignant human cells. Proc. Natl. Acad. Sci. USA, 2004, 101(8), 2253-2258.
[http://dx.doi.org/10.1073/pnas.0308411100] [PMID: 14982996]
[110]
Clague, M.J.; Urbé, S.; Komander, D. Breaking the chains: deubiquitylating enzyme specificity begets function. Nat. Rev. Mol. Cell Biol., 2019, 20(6), 338-352.
[http://dx.doi.org/10.1038/s41580-019-0099-1] [PMID: 30733604]
[111]
Grou, C.P.; Pinto, M.P.; Mendes, A.V.; Domingues, P.; Azevedo, J.E. The de novo synthesis of ubiquitin: identification of deubiquitinases acting on ubiquitin precursors. Sci. Rep., 2015, 5(1), 12836.
[http://dx.doi.org/10.1038/srep12836] [PMID: 26235645]
[112]
Verma, R.; Aravind, L.; Oania, R.; McDonald, W.H.; Yates, J.R., III; Koonin, E.V.; Deshaies, R.J. Role of Rpn11 metalloprotease in deubiquitination and degradation by the 26S proteasome. Science, 2002, 298(5593), 611-615.
[http://dx.doi.org/10.1126/science.1075898] [PMID: 12183636]
[113]
Shi, K.; Zhang, J.Z.; Zhao, R.L.; Yang, L.; Guo, D. PSMD7 downregulation induces apoptosis and suppresses tumorigenesis of esophageal squamous cell carcinoma via the mTOR/p70S6K pathway. FEBS Open Bio, 2018, 8(4), 533-543.
[http://dx.doi.org/10.1002/2211-5463.12394] [PMID: 29632807]
[114]
Chadchankar, J.; Korboukh, V.; Conway, L.C.; Wobst, H.J.; Walker, C.A.; Doig, P.; Jacobsen, S.J.; Brandon, N.J.; Moss, S.J.; Wang, Q. Inactive USP14 and inactive UCHL5 cause accumulation of distinct ubiquitinated proteins in mammalian cells. PLoS One, 2019, 14(11), e0225145.
[http://dx.doi.org/10.1371/journal.pone.0225145] [PMID: 31703099]
[115]
Kimura, Y.; Tanaka, K. Regulatory mechanisms involved in the control of ubiquitin homeostasis. J. Biochem., 2010, 147(6), 793-798.
[http://dx.doi.org/10.1093/jb/mvq044] [PMID: 20418328]
[116]
Lai, K.P.; Chen, J.; Tse, W.K.F. Role of deubiquitinases in human cancers: Potential targeted therapy. Int. J. Mol. Sci., 2020, 21(7), 2548.
[http://dx.doi.org/10.3390/ijms21072548] [PMID: 32268558]
[117]
Fu, C.; Zhu, X.; Xu, P.; Li, Y. Pharmacological inhibition of USP7 promotes antitumor immunity and contributes to colon cancer therapy. OncoTargets Ther., 2019, 12, 609-617.
[http://dx.doi.org/10.2147/OTT.S182806] [PMID: 30697058]
[118]
Claiborn, K.C.; Sachdeva, M.M.; Cannon, C.E.; Groff, D.N.; Singer, J.D.; Stoffers, D.A. Pcif1 modulates Pdx1 protein stability and pancreatic β cell function and survival in mice. J. Clin. Invest., 2010, 120(10), 3713-3721.
[http://dx.doi.org/10.1172/JCI40440] [PMID: 20811152]
[119]
Humphrey, R.K.; Yu, S.M.; Flores, L.E.; Jhala, U.S. Glucose regulates steady-state levels of PDX1 via the reciprocal actions of GSK3 and AKT kinases. J. Biol. Chem., 2010, 285(5), 3406-3416.
[120]
van Arensbergen, J.; García-Hurtado, J.; Maestro, M.A. Ring1b bookmarks genes in pancreatic embryonic progenitors for repression in adult β cells. Genes Dev., 2013, 27(1), 52-63.
[http://dx.doi.org/10.1101/gad.206094.112] [PMID: 23271347]
[121]
Horn, S.; Kobberup, S.; Jørgensen, M.C.; Kalisz, M.; Klein, T.; Kageyama, R.; Gegg, M.; Lickert, H.; Lindner, J.; Magnuson, M.A.; Kong, Y.Y.; Serup, P.; Ahnfelt-Rønne, J.; Jensen, J.N. Mind bomb 1 is required for pancreatic β-cell formation. Proc. Natl. Acad. Sci. USA, 2012, 109(19), 7356-7361.
[http://dx.doi.org/10.1073/pnas.1203605109] [PMID: 22529374]
[122]
Kanai, K.; Aramata, S.; Katakami, S.; Yasuda, K.; Kataoka, K. Proteasome activator PA28gamma stimulates degradation of GSK3-phosphorylated insulin transcription activator MAFA. J. Mol. Endocrinol., 2011, 47(1), 119-127.
[http://dx.doi.org/10.1530/JME-11-0044] [PMID: 21646385]
[123]
Sancho, R.; Gruber, R.; Gu, G.; Behrens, A. Loss of Fbw7 reprograms adult pancreatic ductal cells into α, δ, and β cells. Cell Stem Cell, 2014, 15(2), 139-153.
[http://dx.doi.org/10.1016/j.stem.2014.06.019] [PMID: 25105579]
[124]
Roark, R.; Itzhaki, L.; Philpott, A. Complex regulation controls Neurogenin3 proteolysis. Biol. Open, 2012, 1(12), 1264-1272.
[http://dx.doi.org/10.1242/bio.20121750] [PMID: 23259061]
[125]
Gorrepati, K.D.; He, W.; Lupse, B.; Yuan, T.; Maedler, K.; Ardestani, A. An SCF-FBXO28 E3 ligase protects pancreatic β-cells from apoptosis. Int. J. Mol. Sci., 2018, 19(4), 975.
[http://dx.doi.org/10.3390/ijms19040975] [PMID: 29587369]
[126]
Kawaguchi, M.; Minami, K.; Nagashima, K.; Seino, S. Essential role of ubiquitin-proteasome system in normal regulation of insulin secretion. J. Biol. Chem., 2006, 281(19), 13015-13020.
[127]
Bugliani, M.; Liechti, R.; Cheon, H. Microarray analysis of isolated human islet transcriptome in type 2 diabetes and the role of the ubiquitin-proteasome system in pancreatic beta cell dysfunction. Mol. Cell. Endocrinol., 2013, 367(1-2), 1-10.
[http://dx.doi.org/10.1016/j.mce.2012.12.001] [PMID: 23246353]
[128]
Hunter, C.S.; Stein, R.W. Evidence for loss in identity, de-differentiation, and trans-differentiation of islet β-cells in type 2 diabetes. Front. Genet., 2017, 8, 35.
[http://dx.doi.org/10.3389/fgene.2017.00035] [PMID: 28424732]
[129]
Wang, Z.; York, N.W.; Nichols, C.G.; Remedi, M.S. Pancreatic β cell dedifferentiation in diabetes and redifferentiation following insulin therapy. Cell Metab., 2014, 19(5), 872-882.
[http://dx.doi.org/10.1016/j.cmet.2014.03.010] [PMID: 24746806]
[130]
Kato, S.; Ding, J.; Pisck, E.; Jhala, U.S.; Du, K. COP1 functions as a FoxO1 ubiquitin E3 ligase to regulate FoxO1-mediated gene expression. J. Biol. Chem., 2008, 283(51), 35464-35473.
[http://dx.doi.org/10.1074/jbc.M801011200] [PMID: 18815134]
[131]
Puri, S.; Akiyama, H.; Hebrok, M. VHL-mediated disruption of Sox9 activity compromises β-cell identity and results in diabetes mellitus. Genes Dev., 2013, 27(23), 2563-2575.
[http://dx.doi.org/10.1101/gad.227785.113] [PMID: 24298056]
[132]
Dallavalle, C.; Thalmann, G.; Catapano, C.V.; Carbone, G.M. The E3 ubiquitin ligase COP1 controls STAT3 turnover and its loss leads to increased STAT3 stabilization and activation in prostate cancer. Cancer Res., 2016, (Jul), 4545-4545.
[133]
Lineberry, N.; Su, L.; Soares, L.; Fathman, C.G. The single subunit transmembrane E3 ligase gene related to anergy in lymphocytes (GRAIL) captures and then ubiquitinates transmembrane proteins across the cell membrane. J. Biol. Chem., 2008, 283(42), 28497-28505.
[http://dx.doi.org/10.1074/jbc.M805092200] [PMID: 18713730]
[134]
Eura, Y.; Miyata, T.; Kokame, K. Derlin-3 is required for changes in ERAD complex formation under ER stress. Int. J. Mol. Sci., 2020, 21(17), 6146.
[http://dx.doi.org/10.3390/ijms21176146] [PMID: 32858914]
[135]
Wu, T.; Zhang, S.; Xu, J.; Zhang, Y.; Sun, T.; Shao, Y.; Wang, J.; Tang, W.; Chen, F.; Han, X. HRD1, an important player in pancreatic β-cell failure and therapeutic target for type 2 diabetic mice. Diabetes, 2020, 69(5), 940-953.
[http://dx.doi.org/10.2337/db19-1060] [PMID: 32086291]
[136]
Shrestha, N.; Liu, T.; Ji, Y.; Reinert, R.B.; Torres, M.; Li, X.; Zhang, M.; Tang, C.A.; Hu, C.A.; Liu, C.; Naji, A.; Liu, M.; Lin, J.D.; Kersten, S.; Arvan, P.; Qi, L. Sel1L-Hrd1 ER-associated degradation maintains β cell identity via TGF-β signaling. J. Clin. Invest., 2020, 130(7), 3499-3510.
[http://dx.doi.org/10.1172/JCI134874] [PMID: 32182217]
[137]
Muralidharan, C.; Conteh, A.M.; Marasco, M.R.; Crowder, J.J.; Kuipers, J.; de Boer, P.; Linnemann, A.K. Pancreatic beta cell autophagy is impaired in type 1 diabetes. Diabetologia, 2021, 64(4), 865-877.
[http://dx.doi.org/10.1007/s00125-021-05387-6] [PMID: 33515072]
[138]
Chen, R.H.; Chen, Y.H.; Huang, T.Y. Ubiquitin-mediated regulation of autophagy. J. Biomed. Sci., 2019, 26(1), 80.
[http://dx.doi.org/10.1186/s12929-019-0569-y] [PMID: 31630678]
[139]
Lee, S.H.; Du, J.; Hwa, J.; Kim, W.H. Parkin coordinates platelet stress response in diabetes mellitus: a big role in a small cell. Int. J. Mol. Sci., 2020, 21(16), 5869.
[http://dx.doi.org/10.3390/ijms21165869] [PMID: 32824240]
[140]
Soleimanpour, S.A.; Gupta, A.; Bakay, M.; Ferrari, A.M.; Groff, D.N.; Fadista, J.; Spruce, L.A.; Kushner, J.A.; Groop, L.; Seeholzer, S.H.; Kaufman, B.A.; Hakonarson, H.; Stoffers, D.A. The diabetes susceptibility gene Clec16a regulates mitophagy. Cell, 2014, 157(7), 1577-1590.
[http://dx.doi.org/10.1016/j.cell.2014.05.016] [PMID: 24949970]
[141]
Nostro, M.C.; Sarangi, F.; Ogawa, S.; Holtzinger, A.; Corneo, B.; Li, X.; Micallef, S.J.; Park, I.H.; Basford, C.; Wheeler, M.B.; Daley, G.Q.; Elefanty, A.G.; Stanley, E.G.; Keller, G. Stage-specific signaling through TGFβ family members and WNT regulates patterning and pancreatic specification of human pluripotent stem cells. Development, 2011, 138(5), 861-871.
[http://dx.doi.org/10.1242/dev.055236] [PMID: 21270052]
[142]
Kit Leng Lui, S.; Iyengar, P.V.; Jaynes, P.; Isa, Z.F.B.A.; Pang, B.; Tan, T.Z.; Eichhorn, P.J.A. USP26 regulates TGF-β signaling by deubiquitinating and stabilizing SMAD7. EMBO Rep., 2017, 18(5), 797-808.
[http://dx.doi.org/10.15252/embr.201643270] [PMID: 28381482]
[143]
Zhang, L.; Zhou, F.; Drabsch, Y.; Gao, R.; Snaar-Jagalska, B.E.; Mickanin, C.; Huang, H.; Sheppard, K.A.; Porter, J.A.; Lu, C.X.; ten Dijke, P. USP4 is regulated by AKT phosphorylation and directly deubiquitylates TGF-β type I receptor. Nat. Cell Biol., 2012, 14(7), 717-726.
[http://dx.doi.org/10.1038/ncb2522] [PMID: 22706160]
[144]
Eichhorn, P.J.; Rodón, L.; Gonzàlez-Juncà, A.; Dirac, A.; Gili, M.; Martínez-Sáez, E.; Aura, C.; Barba, I.; Peg, V.; Prat, A.; Cuartas, I.; Jimenez, J.; García-Dorado, D.; Sahuquillo, J.; Bernards, R.; Baselga, J.; Seoane, J. USP15 stabilizes TGF-β receptor I and promotes oncogenesis through the activation of TGF-β signaling in glioblastoma. Nat. Med., 2012, 18(3), 429-435.
[http://dx.doi.org/10.1038/nm.2619] [PMID: 22344298]
[145]
Ibarrola, N.; Kratchmarova, I.; Nakajima, D.; Schiemann, W.P.; Moustakas, A.; Pandey, A.; Mann, M. Cloning of a novel signaling molecule, AMSH-2, that potentiates transforming growth factor β signaling. BMC Cell Biol., 2004, 5(1), 2.
[http://dx.doi.org/10.1186/1471-2121-5-2] [PMID: 14728725]
[146]
Lee, H.J. The role of tripartite motif family proteins in TGF-β signaling pathway and cancer. J. Cancer Prev., 2018, 23(4), 162-169.
[http://dx.doi.org/10.15430/JCP.2018.23.4.162] [PMID: 30671398]
[147]
Suzuki, C.; Murakami, G.; Fukuchi, M.; Shimanuki, T.; Shikauchi, Y.; Imamura, T.; Miyazono, K. Smurf1 regulates the inhibitory activity of Smad7 by targeting Smad7 to the plasma membrane. J. Biol. Chem., 2002, 277(42), 39919-39925.
[http://dx.doi.org/10.1074/jbc.M201901200] [PMID: 12151385]
[148]
Cui, Y.; He, S.; Xing, C.; Lu, K.; Wang, J.; Xing, G.; Meng, A.; Jia, S.; He, F.; Zhang, L. SCFFBXL15 regulates BMP signalling by directing the degradation of HECT-type ubiquitin ligase Smurf1. EMBO J., 2011, 30(13), 2675-2689.
[http://dx.doi.org/10.1038/emboj.2011.155] [PMID: 21572392]
[149]
Xie, Y.; Avello, M.; Schirle, M.; McWhinnie, E.; Feng, Y.; Bric-Furlong, E.; Wilson, C.; Nathans, R.; Zhang, J.; Kirschner, M.W.; Huang, S.M.; Cong, F. Deubiquitinase FAM/USP9X interacts with the E3 ubiquitin ligase SMURF1 protein and protects it from ligase activity-dependent self-degradation. J. Biol. Chem., 2013, 288(5), 2976-2985.
[http://dx.doi.org/10.1074/jbc.M112.430066] [PMID: 23184937]
[150]
Fraile, J.M.; Quesada, V.; Rodríguez, D.; Freije, J.M.; López-Otín, C. Deubiquitinases in cancer: New functions and therapeutic options. Oncogene, 2012, 31(19), 2373-2388.
[http://dx.doi.org/10.1038/onc.2011.443] [PMID: 21996736]
[151]
Zhou, A.; Lin, K.; Zhang, S.; Ma, L.; Xue, J.; Morris, S.A.; Aldape, K.D.; Huang, S. Gli1-induced deubiquitinase USP48 aids glioblastoma tumorigenesis by stabilizing Gli1. EMBO Rep., 2017, 18(8), 1318-1330.
[http://dx.doi.org/10.15252/embr.201643124] [PMID: 28623188]
[152]
Zhu, R.; Gires, O.; Zhu, L.; Liu, J.; Li, J.; Yang, H.; Ju, G.; Huang, J.; Ge, W.; Chen, Y.; Lu, Z.; Wang, H. TSPAN8 promotes cancer cell stemness via activation of sonic Hedgehog signaling. Nat. Commun., 2019, 10(1), 2863.
[http://dx.doi.org/10.1038/s41467-019-10739-3] [PMID: 31253779]
[153]
Desgraz, R.; Herrera, P.L. Pancreatic neurogenin 3-expressing cells are unipotent islet precursors. Development, 2009, 136(21), 3567-3574.
[http://dx.doi.org/10.1242/dev.039214] [PMID: 19793886]
[154]
DiNicolantonio, J.J.; McCarty, M. Autophagy-induced degradation of Notch1, achieved through intermittent fasting, may promote beta cell neogenesis: implications for reversal of type 2 diabetes. Open Heart, 2019, 6(1), e001028.
[http://dx.doi.org/10.1136/openhrt-2019-001028] [PMID: 31218007]
[155]
Premarathne, S.; Murtaza, M.; Matigian, N.; Jolly, L.A.; Wood, S.A. Loss of Usp9x disrupts cell adhesion, and components of the Wnt and Notch signaling pathways in neural progenitors. Sci. Rep., 2017, 7(1), 8109.
[http://dx.doi.org/10.1038/s41598-017-05451-5] [PMID: 28808228]
[156]
Sonego, M.; Pellarin, I.; Costa, A.; Vinciguerra, G.L.R.; Coan, M.; Kraut, A.; D’Andrea, S.; Dall’Acqua, A.; Castillo-Tong, D.C.; Califano, D.; Losito, S.; Spizzo, R.; Couté, Y.; Vecchione, A.; Belletti, B.; Schiappacassi, M.; Baldassarre, G. USP1 links platinum resistance to cancer cell dissemination by regulating Snail stability. Sci. Adv., 2019, 5(5), eaav3235.
[http://dx.doi.org/10.1126/sciadv.aav3235] [PMID: 31086816]
[157]
Seeberger, K.L.; Anderson, S.J.; Ellis, C.E.; Yeung, T.Y.; Korbutt, G.S. Identification and differentiation of PDX1 β-cell progenitors within the human pancreatic epithelium. World J. Diabetes, 2014, 5(1), 59-68.
[http://dx.doi.org/10.4239/wjd.v5.i1.59] [PMID: 24567802]
[158]
He, Y.; Wang, S.; Tong, J.; Jiang, S.; Yang, Y.; Zhang, Z.; Xu, Y.; Zeng, Y.; Cao, B.; Moran, M.F.; Mao, X. The deubiquitinase USP7 stabilizes Maf proteins to promote myeloma cell survival. J. Biol. Chem., 2020, 295(7), 2084-2096.
[http://dx.doi.org/10.1074/jbc.RA119.010724] [PMID: 31822558]
[159]
Zhou, H.; Liu, Y.; Zhu, R.; Ding, F.; Cao, X.; Lin, D.; Liu, Z. OTUB1 promotes esophageal squamous cell carcinoma metastasis through modulating Snail stability. Oncogene, 2018, 37(25), 3356-3368.
[http://dx.doi.org/10.1038/s41388-018-0224-1] [PMID: 29559747]
[160]
Wu, Y; Wang, Y; Lin, Y Dub3 inhibition suppresses breast cancer invasion and metastasis by promoting Snail1 degradation. Nat comm., 2017, 8(1), 1-6.
[http://dx.doi.org/10.1038/ncomms14228]
[161]
Cai, J.; Li, M.; Wang, X.; Li, L.; Li, Q.; Hou, Z.; Jia, H.; Liu, S. USP37 promotes lung cancer cell migration by stabilizing Snail protein via deubiquitination. Front. Genet., 2020, 10, 1324.
[http://dx.doi.org/10.3389/fgene.2019.01324] [PMID: 31998374]
[162]
Lin, Y.; Wang, Y.; Shi, Q.; Yu, Q.; Liu, C.; Feng, J.; Deng, J.; Evers, B.M.; Zhou, B.P.; Wu, Y. Stabilization of the transcription factors slug and twist by the deubiquitinase dub3 is a key requirement for tumor metastasis. Oncotarget, 2017, 8(43), 75127-75140.
[http://dx.doi.org/10.18632/oncotarget.20561] [PMID: 29088851]
[163]
Hasnain, S.Z.; Prins, J.B.; McGuckin, M.A. Oxidative and endoplasmic reticulum stress in β-cell dysfunction in diabetes. J. Mol. Endocrinol., 2016, 56(2), R33-R54.
[http://dx.doi.org/10.1530/JME-15-0232] [PMID: 26576641]
[164]
Eguchi, N.; Vaziri, N.D.; Dafoe, D.C.; Ichii, H. The role of oxidative stress in pancreatic β cell dysfunction in diabetes. Int. J. Mol. Sci., 2021, 22(4), 1509.
[http://dx.doi.org/10.3390/ijms22041509] [PMID: 33546200]
[165]
Cotto-Rios, X.M.; Békés, M.; Chapman, J.; Ueberheide, B.; Huang, T.T. Deubiquitinases as a signaling target of oxidative stress. Cell Rep., 2012, 2(6), 1475-1484.
[http://dx.doi.org/10.1016/j.celrep.2012.11.011] [PMID: 23219552]
[166]
Diao, W.; Guo, Q.; Zhu, C.; Song, Y.; Feng, H.; Cao, Y.; Du, M.; Chen, H. USP18 promotes cell proliferation and suppressed apoptosis in cervical cancer cells via activating AKT signaling pathway. BMC Cancer, 2020, 20(1), 741.
[http://dx.doi.org/10.1186/s12885-020-07241-1] [PMID: 32770981]
[167]
Lai, K.P.; Cheung, A.H.Y.; Tse, W.K.F. Deubiquitinase Usp18 prevents cellular apoptosis from oxidative stress in liver cells. Cell Biol. Int., 2017, 41(8), 914-921.
[http://dx.doi.org/10.1002/cbin.10799] [PMID: 28557172]
[168]
Santin, I.; Moore, F.; Grieco, F.A.; Marchetti, P.; Brancolini, C.; Eizirik, D.L. USP18 is a key regulator of the interferon-driven gene network modulating pancreatic beta cell inflammation and apoptosis. Cell Death Dis., 2012, 3(11), e419.
[http://dx.doi.org/10.1038/cddis.2012.158] [PMID: 23152055]
[169]
Basters, A.; Knobeloch, K.P.; Fritz, G. USP18 - a multifunctional component in the interferon response. Biosci. Rep., 2018, 38(6), BSR20180250.
[http://dx.doi.org/10.1042/BSR20180250] [PMID: 30126853]
[170]
Cheng, K.; Ho, K.; Stokes, R.; Scott, C.; Lau, S.M.; Hawthorne, W.J.; O’Connell, P.J.; Loudovaris, T.; Kay, T.W.; Kulkarni, R.N.; Okada, T.; Wang, X.L.; Yim, S.H.; Shah, Y.; Grey, S.T.; Biankin, A.V.; Kench, J.G.; Laybutt, D.R.; Gonzalez, F.J.; Kahn, C.R.; Gunton, J.E. Hypoxia-inducible factor-1α regulates β cell function in mouse and human islets. J. Clin. Invest., 2010, 120(6), 2171-2183.
[http://dx.doi.org/10.1172/JCI35846] [PMID: 20440072]
[171]
Lalwani, A.; Warren, J.; Liuwantara, D.; Hawthorne, W.J.; O’Connell, P.J.; Gonzalez, F.J.; Stokes, R.A.; Chen, J.; Laybutt, D.R.; Craig, M.E.; Swarbrick, M.M.; King, C.; Gunton, J.E. β Cell hypoxia-inducible factor-1α is required for the prevention of type 1 diabetes. Cell Rep., 2019, 27(8), 2370-2384.
[http://dx.doi.org/10.1016/j.celrep.2019.04.086] [PMID: 31116982]
[172]
Schober, A.S.; Berra, E. DUBs, new members in the hypoxia signaling clUb. Front. Oncol., 2016, 6, 53.
[http://dx.doi.org/10.3389/fonc.2016.00053] [PMID: 27014628]
[173]
Li, Z.; Wang, D.; Messing, E.M.; Wu, G. VHL protein-interacting deubiquitinating enzyme 2 deubiquitinates and stabilizes HIF-1α. EMBO Rep., 2005, 6(4), 373-378.
[http://dx.doi.org/10.1038/sj.embor.7400377] [PMID: 15776016]
[174]
Flügel, D.; Görlach, A.; Kietzmann, T. GSK-3β regulates cell growth, migration, and angiogenesis via Fbw7 and USP28-dependent degradation of HIF-1α. Blood, 2012, 119(5), 1292-1301.
[http://dx.doi.org/10.1182/blood-2011-08-375014] [PMID: 22144179]
[175]
Xiang, T.; Li, L.; Yin, X.; Yuan, C.; Tan, C.; Su, X.; Xiong, L.; Putti, T.C.; Oberst, M.; Kelly, K.; Ren, G.; Tao, Q. The ubiquitin peptidase UCHL1 induces G0/G1 cell cycle arrest and apoptosis through stabilizing p53 and is frequently silenced in breast cancer. PLoS One, 2012, 7(1), e29783.
[http://dx.doi.org/10.1371/journal.pone.0029783] [PMID: 22279545]
[176]
Li, S.; Zheng, H.; Mao, A.P.; Zhong, B.; Li, Y.; Liu, Y.; Gao, Y.; Ran, Y.; Tien, P.; Shu, H.B. Regulation of virus-triggered signaling by OTUB1- and OTUB2-mediated deubiquitination of TRAF3 and TRAF6. J. Biol. Chem., 2010, 285(7), 4291-4297.
[http://dx.doi.org/10.1074/jbc.M109.074971] [PMID: 19996094]
[177]
Gorrepati, K.D.D.; Lupse, B.; Annamalai, K.; Yuan, T.; Maedler, K.; Ardestani, A. Loss of deubiquitinase USP1 blocks pancreatic β-cell apoptosis by inhibiting DNA damage response. iScience, 2018, 1, 72-86.
[http://dx.doi.org/10.1016/j.isci.2018.02.003] [PMID: 30227958]
[178]
Das, D.S.; Das, A.; Ray, A.; Song, Y.; Samur, M.K.; Munshi, N.C.; Chauhan, D.; Anderson, K.C. Blockade of deubiquitylating enzyme USP1 inhibits DNA repair and triggers apoptosis in multiple myeloma cells. Clin. Cancer Res., 2017, 23(15), 4280-4289.
[http://dx.doi.org/10.1158/1078-0432.CCR-16-2692] [PMID: 28270494]
[179]
Tyka, K.; Jörns, A.; Turatsinze, J.V.; Eizirik, D.L.; Lenzen, S.; Gurgul-Convey, E. MCPIP1 regulates the sensitivity of pancreatic beta-cells to cytokine toxicity. Cell Death Dis., 2019, 10(1), 29.
[http://dx.doi.org/10.1038/s41419-018-1268-4] [PMID: 30631045]
[180]
Pearson, G.; Soleimanpour, S.A. A ubiquitin-dependent mitophagy complex maintains mitochondrial function and insulin secretion in beta cells. Autophagy, 2018, 14(7), 1160-1161.
[http://dx.doi.org/10.1080/15548627.2018.1446627] [PMID: 29799764]
[181]
Pearson, G.; Chai, B.; Vozheiko, T.; Liu, X.; Kandarpa, M.; Piper, R.C.; Soleimanpour, S.A. Clec16a, Nrdp1, and USP8 form a ubiquitin-dependent tripartite complex that regulates β-cell mitophagy. Diabetes, 2018, 67(2), 265-277.
[http://dx.doi.org/10.2337/db17-0321] [PMID: 29180353]
[182]
Sachs, S.; Bastidas-Ponce, A.; Tritschler, S.; Bakhti, M.; Böttcher, A.; Sánchez-Garrido, M.A.; Tarquis-Medina, M.; Kleinert, M.; Fischer, K.; Jall, S.; Harger, A.; Bader, E.; Roscioni, S.; Ussar, S.; Feuchtinger, A.; Yesildag, B.; Neelakandhan, A.; Jensen, C.B.; Cornu, M.; Yang, B.; Finan, B.; DiMarchi, R.D.; Tschöp, M.H.; Theis, F.J.; Hofmann, S.M.; Müller, T.D.; Lickert, H. Targeted pharmacological therapy restores β-cell function for diabetes remission. Nat. Metab., 2020, 2(2), 192-209.
[http://dx.doi.org/10.1038/s42255-020-0171-3] [PMID: 32694693]
[183]
Burke, S.J.; Batdorf, H.M.; Burk, D.H.; Martin, T.M.; Mendoza, T.; Stadler, K.; Alami, W.; Karlstad, M.D.; Robson, M.J.; Blakely, R.D.; Mynatt, R.L.; Collier, J.J. Pancreatic deletion of the interleukin-1 receptor disrupts whole body glucose homeostasis and promotes islet β-cell de-differentiation. Mol. Metab., 2018, 14, 95-107.
[http://dx.doi.org/10.1016/j.molmet.2018.06.003] [PMID: 29914854]
[184]
Wang, L.; Liu, T.; Liang, R.; Wang, G.; Liu, Y.; Zou, J.; Liu, N.; Zhang, B.; Liu, Y.; Ding, X.; Cai, X.; Wang, Z.; Xu, X.; Ricordi, C.; Wang, S.; Shen, Z. Mesenchymal stem cells ameliorate β cell dysfunction of human type 2 diabetic islets by reversing β cell dedifferentiation. EBioMedicine, 2020, 51, 102615.
[http://dx.doi.org/10.1016/j.ebiom.2019.102615] [PMID: 31918404]
[185]
Ee, G.; Lehming, N. How the ubiquitin proteasome system regulates the regulators of transcription. Transcription, 2012, 3(5), 235-239.
[http://dx.doi.org/10.4161/trns.21249] [PMID: 22885980]
[186]
Paiva, S.L.; Crews, C.M. Targeted protein degradation: elements of PROTAC design. Curr. Opin. Chem. Biol., 2019, 50, 111-119.
[http://dx.doi.org/10.1016/j.cbpa.2019.02.022] [PMID: 31004963]
[187]
Li, W.; Li, F.; Lei, W.; Tao, Z. TRIM30 modulates Interleukin-22-regulated papillary thyroid Cancer cell migration and invasion by targeting Sox17 for K48-linked Polyubiquitination. Cell Commun. Signal., 2019, 17(1), 162.
[http://dx.doi.org/10.1186/s12964-019-0484-6] [PMID: 31823782]
[188]
Marchese, A.; Raiborg, C.; Santini, F.; Keen, J.H.; Stenmark, H.; Benovic, J.L. The E3 ubiquitin ligase AIP4 mediates ubiquitination and sorting of the G protein-coupled receptor CXCR4. Dev. Cell, 2003, 5(5), 709-722.
[http://dx.doi.org/10.1016/S1534-5807(03)00321-6] [PMID: 14602072]
[189]
Zhan, F.; Zhong, Y.; Qin, Y.; Li, L.; Wu, W.; Yao, M. SND1 facilitates the invasion and migration of cervical cancer cells by Smurf1-mediated degradation of FOXA2. Exp. Cell Res., 2020, 388(1), 111809.
[http://dx.doi.org/10.1016/j.yexcr.2019.111809] [PMID: 31891682]
[190]
Hanoun, N.; Fritsch, S.; Gayet, O.; Gigoux, V.; Cordelier, P.; Dusetti, N.; Torrisani, J.; Dufresne, M. The E3 ubiquitin ligase thyroid hormone receptor-interacting protein 12 targets pancreas transcription factor 1a for proteasomal degradation. J. Biol. Chem., 2014, 289(51), 35593-35604.
[http://dx.doi.org/10.1074/jbc.M114.620104] [PMID: 25355311]
[191]
Suryo Rahmanto, A.; Savov, V.; Brunner, A.; Bolin, S.; Weishaupt, H.; Malyukova, A.; Rosén, G.; Čančer, M.; Hutter, S.; Sundström, A.; Kawauchi, D.; Jones, D.T.; Spruck, C.; Taylor, M.D.; Cho, Y.J.; Pfister, S.M.; Kool, M.; Korshunov, A.; Swartling, F.J.; Sangfelt, O. FBW7 suppression leads to SOX9 stabilization and increased malignancy in medulloblastoma. EMBO J., 2016, 35(20), 2192-2212.
[http://dx.doi.org/10.15252/embj.201693889] [PMID: 27625374]
[192]
Tuoc, T.C.; Stoykova, A. Trim11 modulates the function of neurogenic transcription factor Pax6 through ubiquitin-proteosome system. Genes Dev., 2008, 22(14), 1972-1986.
[http://dx.doi.org/10.1101/gad.471708] [PMID: 18628401]
[193]
Jang, J.W.; Lee, W.Y.; Lee, J.H.; Moon, S.H.; Kim, C.H.; Chung, H.M. A novel Fbxo25 acts as an E3 ligase for destructing cardiac specific transcription factors. Biochem. Biophys. Res. Commun., 2011, 410(2), 183-188.
[http://dx.doi.org/10.1016/j.bbrc.2011.05.011] [PMID: 21596019]
[194]
ZeRuth. G.T.; Williams, J.G.; Cole, Y.C.; Jetten, A.M. HECT E3 ubiquitin ligase itch functions as a novel negative regulator of Gli-Similar 3 (Glis3) transcriptional activity. PLoS One, 2015, 10(7), e0131303.
[http://dx.doi.org/10.1371/journal.pone.0131303] [PMID: 26147758]
[195]
Izrailit, J.; Jaiswal, A.; Zheng, W.; Moran, M.F.; Reedijk, M. Cellular stress induces TRB3/USP9x-dependent Notch activation in cancer. Oncogene, 2017, 36(8), 1048-1057.
[http://dx.doi.org/10.1038/onc.2016.276] [PMID: 27593927]
[196]
Nakashima, R.; Goto, Y.; Koyasu, S.; Kobayashi, M.; Morinibu, A.; Yoshimura, M.; Hiraoka, M.; Hammond, E.M.; Harada, H. UCHL1-HIF-1 axis-mediated antioxidant property of cancer cells as a therapeutic target for radiosensitization. Sci. Rep., 2017, 7(1), 6879.
[http://dx.doi.org/10.1038/s41598-017-06605-1] [PMID: 28761052]

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