Akt phosphorylates the transcriptional repressor Bmi1 to block its effects on the tumor-suppressing Ink4a-Arf locus Academic Article uri icon

Overview

MeSH Major

  • Cyclin-Dependent Kinase Inhibitor p16
  • Genetic Loci
  • Polycomb Repressive Complex 1
  • Proto-Oncogene Proteins
  • Proto-Oncogene Proteins c-akt
  • Repressor Proteins

abstract

  • 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.

publication date

  • October 23, 2012

Research

keywords

  • Academic Article

Identity

Language

  • eng

PubMed Central ID

  • PMC3784651

Digital Object Identifier (DOI)

  • 10.1126/scisignal.2003199

PubMed ID

  • 23092893

Additional Document Info

start page

  • ra77

volume

  • 5

number

  • 247