Fig. 3.

DUBs that modulate the key factors of the DNA damage response leading to different cell fates. USP4 was found to interact with one of the DNA damage sensors MRN complex and the DNA end resection factor CtIP and interfered with CtIP and MRN binding, thus impairing DNA end resection and HR [56]. USP1 and USP7 are reported to be involved in deubiquitination and stabilization of Chk1. USP28 forms a complex with PIRH2 and CHK2 and antagonizes PIRH2-mediated polyubiquitylation and proteasomal degradation of CHK2. Several deubiquitinating enzymes to date have been identified targeting p53 which will be discussed in this review. These DUBs can target p53 directly or indirectly by regulating the E3 ligase Mdm2. DUB3 mediates deubiquitination of CDC25A, preventing CDC25A degradation during the G1/S and G2/M phases, promoting cell-cycle progression [57]