Abstract
The Polycomb group protein Bmi1 is a transcriptional silencer of the Ink4a-Arf locus, which encodes the cell cycle regulator p16Ink4a and the tumor suppressor p19Arf. 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 ofBmi1 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 mechanismfor the increased abundance of p16Ink4a and p19Arfseen in cancer cells with an activated phosphoinositide 3-kinase to Akt signaling pathway and identifies crosstalk between phosphorylation events and chromatin structure.
Original language | English (US) |
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Article number | ra77 |
Journal | Science signaling |
Volume | 5 |
Issue number | 247 |
DOIs | |
State | Published - Oct 23 2012 |
Externally published | Yes |
ASJC Scopus subject areas
- Molecular Biology
- Biochemistry
- Cell Biology