Abstract
E2F1 is a critical transcription factor that regulates cell cycle progression, is expressed at high levels in most cancer cells, and activates the biogenesis of proteins related to the cell cycle. Over recent years, researchers have demonstrated that E2F1 could also facilitate cellular apoptosis under conditions of cellular stress, thus creating a double-edged sword associated with both the regulation of cellular survival and death. However, the mechanisms responsible for these actions remain poorly understood. In this study, we demonstrated that serum stress could activate the acetylation of E2F1 at K125. Further analysis indicated that the acetylation of E2F1 at K125 could facilitate its interaction with the promoter of FAS and upregulate the levels of Fas. Furthermore, the acetylation of E2F1 attenuated its interaction with p53, thus leading to the transactivation of BAX. The upregulation of Fas and Bax activated the cleavage of caspase-3 and facilitated the apoptosis of HCC cells experiencing serum stress. Collectively, our findings indicated that the acetylation of E2F1 at K125 under serum stress leads to a functional change and a new role as an executor of cell death instead of an oncoprotein.