SIRT7 activates p53 by enhancing PCAF-mediated MDM2 degradation to arrest the cell cycle

Ya-Fei Lu, Xiao-Peng Xu, Xiao-Peng Lu, Qian Zhu, Ge Liu, Yan-Tao Bao, He Wen, Ying-Lu Li, Wei Gu, Wei-Guo Zhu
2020 Oncogene  
Sirtuin 7 (SIRT7), an NAD+-dependent deacetylase, plays vital roles in energy sensing, but the underlying mechanisms of action remain less clear. Here, we report that SIRT7 is required for p53-dependent cell-cycle arrest during glucose deprivation. We show that SIRT7 directly interacts with p300/CBP-associated factor (PCAF) and the affinity for this interaction increases during glucose deprivation. Upon binding, SIRT7 deacetylates PCAF at lysine 720 (K720), which augments PCAF binding to murine
more » ... double minute (MDM2), the p53 E3 ubiquitin ligase, leading to accelerated MDM2 degradation. This effect results in upregulated expression of the cell-cycle inhibitor, p21Waf1/Cip1, which further leads to cell-cycle arrest and decreased cell viability. These data highlight the importance of the SIRT7-PCAF interaction in regulating p53 activity and cell-cycle progression during conditions of glucose deprivation. This axis may represent a new avenue to design effective therapeutics based on tumor starvation.
doi:10.1038/s41388-020-1305-5 pmid:32404984 fatcat:52j42ewjbjc7dfhkl2wemvn2fm