Browsing by Author "Deblasio, Anthony"

Now showing 1 - 1 of 1
  • Thumbnail Image
    Item
    Akt Phosphorylates the Transcriptional Repressor Bmi1 to Block Its Effects on the Tumor-Suppressing Ink4a-Arf Locus
    (American Association for the Advancement of Science, 2012-10-23) Liu, Yan; Liu, Fan; Yu, Hao; Zhao, Xinyang; Sashida, Goro; Deblasio, Anthony; Harr, Michael; She, Qing-Bai; Chen, Zhenbang; Lin, Hui-Kuan; Di Giandomenico, Silvana; Elf, Shannon E.; Yang, Youyang; Miyata, Yasuhiko; Huang, Gang; Menendez, Silvia; Mellinghoff, Ingo K.; Rosen, Neal; Pandolfi, Pier Paolo; Hedvat, Cyrus V.; Nimer, Stephen D.; Pediatrics, School of Medicine
    The 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.