The Role of the Complex USP1/WDR48 in Differentiation and Proliferation Processes in Cancer Stem Cells

Title:The Role of the Complex USP1/WDR48 in Differentiation and Proliferation Processes in Cancer Stem Cells

Volume: 12 Issue: 5

Author(s): Jussara Maria Goncalves, Mabel Mariela Rodriguez Cordeiro*Elena Riet Correa Rivero

Affiliation:

• Federal University of Santa Catarina, Department of Morphological Sciences, Reitor Joao David Ferreira Lima Campus, Zip Code 88040-900, Florianopolis, Santa Catarina,Brazil

Keywords: Cancer, neoplasms, USP1 protein, WDR48 protein, stem cell, cancer stem cell, ubiquitin, deubiquitinase.

Abstract: Background: Recently, some studies identified the Basic-Helix-Loop-Helix (bHLH) transcription factor as a significant regulator for the evolution of neoplasms. The binding between bHLH proteins and DNA is restricted by heterodimerization with Inhibitors of DNA binding (ID). IDs prevent cellular differentiation, promote growth and sustain tumor development. The wide presence of stem cells in cancers suggests that genes ID are essential to cancer stem cells (CSC) progress. The enzyme Ubiquitin-specific protease 1 (USP1) is reported to deubiquitinate and stabilize IDs. Considering the action of the proteins ID, USP1 contributes to prevent differentiation mediated by bHLH and, consequently, keep CSC original characteristics. USP1 has its activity potentiated when bound to protein WD repeat-containing protein (WDR48).

Objective: To identify the influence of the complex USP1/WDR48 during the CSC tumorigenesis process, and whether this complex is a possible therapeutic target. Methods: A literature search regarding the role of the complex USP1/WDR48 in inhibiting differentiation and increasing proliferation of CSC was performed, and possible selective molecule inhibitors of these deubiquitinase proteins were investigated.

Results: There is evidence that USP1/WDR48 complex promotes stem cell conservation and regulation of DNA damage repair. For this reason, inhibitors as Pimozide, GW7647, C527, SJB2-043, ML323 have been studied to inhibit USPs in cases of treatment intervention.

Conclusion: It is consolidated in the literature the role of USP1/WDR48 during tumorigenesis. However, these studies are not enough to completely clarify the process; but certainly, the researchers are converging towards a promising direction to provide a new treatment option for cancer.

Cite this article as:

Goncalves Maria Jussara, Cordeiro Mariela Rodriguez Mabel *, Rivero Riet Correa Elena , The Role of the Complex USP1/WDR48 in Differentiation and Proliferation Processes in Cancer Stem Cells, Current Stem Cell Research & Therapy 2017; 12 (5) . https://dx.doi.org/10.2174/1574888X12666170315104013

DOI https://dx.doi.org/10.2174/1574888X12666170315104013	Print ISSN 1574-888X
Publisher Name Bentham Science Publisher	Online ISSN 2212-3946