Liu, YanLiu, FanYu, HaoZhao, XinyangSashida, GoroDeblasio, AnthonyHarr, MichaelShe, Qing-BaiChen, ZhenbangLin, Hui-KuanDi Giandomenico, SilvanaElf, Shannon E.Yang, YouyangMiyata, YasuhikoHuang, GangMenendez, SilviaMellinghoff, Ingo K.Rosen, NealPandolfi, Pier PaoloHedvat, Cyrus V.Nimer, Stephen D.2025-06-122025-06-122012-10-23Liu Y, Liu F, Yu H, et al. Akt phosphorylates the transcriptional repressor bmi1 to block its effects on the tumor-suppressing ink4a-arf locus. Sci Signal. 2012;5(247):ra77. Published 2012 Oct 23. doi:10.1126/scisignal.2003199https://hdl.handle.net/1805/48630The Polycomb group protein Bmi1 is a transcriptional silencer of the Ink4a-Arf locus, which encodes the cell cycle regulator p16(Ink4a) and the tumor suppressor p19(Arf). Bmi1 plays a key role in oncogenesis and stem cell self-renewal. We report that phosphorylation of human Bmi1 at Ser³¹⁶ by Akt impaired its function by triggering its dissociation from the Ink4a-Arf locus, which resulted in decreased ubiquitylation of histone H2A and the inability of Bmi1 to promote cellular proliferation and tumor growth. Moreover, Akt-mediated phosphorylation of Bmi1 also inhibited its ability to promote self-renewal of hematopoietic stem and progenitor cells. Our study provides a mechanism for the increased abundance of p16(Ink4a) and p19(Arf) seen in cancer cells with an activated phosphoinositide 3-kinase to Akt signaling pathway and identifies crosstalk between phosphorylation events and chromatin structure.en-USPublisher PolicyProto-oncogene proteinsUbiquitinationChromatinHistonesArticle