TIP60 governs the auto-ubiquitination of UHRF1 through USP7 dissociation from the UHRF1/USP7 complex

Tat interactive protein, 60 kDa (TIP60) is an important partner of ubiquitin-like, containing PHD and RING finger domains 1 (UHRF1), ensuring various cellular processes through its acetyltransferase activity. TIP60 is believed to play a tumor suppressive role, partly explained by its downregulated expression in a number of cancers. The aim of the present study was to investigate the role and mechanisms of action of TIP60 in the regulation of UHRF1 expression. The results revealed that TIP60 overexpression downregulated the UHRF1 and DNA methyltransferase 1 (DNMT1) expression levels. TIP60 interfered with USP7-UHRF1 association and induced the degradation of UHRF1 in an auto-ubiquitination-dependent manner. Moreover, TIP60 activated the p73-mediated apoptotic pathway. Taken together, the data of the present study suggest that the tumor suppressor role of TIP60 is mediated by its regulation to UHRF1.

Automated summary

TIP60 plays a tumor suppressor role by regulating UHRF1 expression, decreasing levels of UHRF1 and DNMT1, disrupting the USP7-UHRF1 association, inducing the degradation of UHRF1 in an auto-ubiquitination-dependent manner, and activating the p73-mediated apoptotic pathway.