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.