Ubiquitin‐Specific Protease 24 Regulates Apoptosis through Deubiquinating Bax and Mediating Ku70 Acetylation

Abstract

Ubiquitin‐specific protease (USP) 24 is one of deubiquinating enzymes (DUBs), which remove polyubiquitin chains from protein substrates and thereby prevent the substrates from ubiquitin‐mediated proteasomal degradation. However, little is so far known about the possible role of USP24 in control of protein deubiquitination or in physiological function. In this study, we used a time‐lapse technique to observe U2OS cells, and we found that USP24 overexpression caused cell death and increased the detection of caspase‐3 cleavage revealed that apoptosis occurred. Furthermore, we we showed that USP24 specifically interacted with and deubiquitinated Bax. USP24 stabilized Bax protein levels, which required its deubiquitinase activity. Moreover, a yeast two‐hybrid screening of a human cDNA library was performed to identify potential USP24 cellular partners. We identified a nonhomologous end‐joining (NHEJ) factor, Ku70, as a likely USP24‐interacting partner. The Ku70 protein was shown to be involved in multiple cellular pathways including DNA repair, telomere maintenance, V(D)J recombination and Bax mediated apoptosis. Here, we found that USP24 could induce Ku70 acetylation via stabilizing p300 protein levels and decrease the interaction between Ku70 and Bax. Taken together, our findings have uncovered an important role of USP24 in regulating apoptosis via deubiquitinating Bax and enhancing Ku70 acetylation to release Bax.