USP28 regulates deubiquitination of histone H2A and cell proliferation.

ABSTRACT

Post-translational modifications of the histone H2A represent an important mechanism by which cells modulate the structure and function of chromatin. Ubiquitination at K119 of histone H2A is associated transcriptional repression, which is shown to be regulated by deubiquitinases (DUBs). Here, we performed a screen to identify novel DUBs for histone H2A. Although RNAi-mediated knockdown of USP28, USP32 and USP36 showed that their depletion resulted in the increase of ub-K119-H2A, only USP28-depleted cells showed increased cell proliferation. Notably, USP28 knockdown cells had decreased expression of p53, p21 and p16INK4a, suggesting that the effect of USP28 on cell proliferation was mediated by regulating the expression of p53, p21 and p16INK4a. In summary, we have shown that USP28 is a deubiquitinase for histone H2A and is involved in regulation of cell proliferation. Thus, USP28 represents a potentially novel therapeutic target for cancer.