TY - JOUR
T1 - Akt phosphorylates the transcriptional repressor Bmi1 to block its effects on the tumor-suppressing Ink4a-Arf locus
AU - Liu, Yan
AU - Liu, Fan
AU - Yu, Hao
AU - Zhao, Xinyang
AU - Sashida, Goro
AU - Deblasio, Anthony
AU - Harr, Michael
AU - She, Qing Bai
AU - Chen, Zhenbang
AU - Lin, Hui Kuan
AU - Di Giandomenico, Silvana
AU - Elf, Shannon E.
AU - Yang, Youyang
AU - Miyata, Yasuhiko
AU - Huang, Gang
AU - Menendez, Silvia
AU - Mellinghoff, Ingo K.
AU - Rosen, Neal
AU - Pandolfi, Pier Paolo
AU - Hedvat, Cyrus V.
AU - Nimer, Stephen D.
PY - 2012/10/23
Y1 - 2012/10/23
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=84868159785&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84868159785&partnerID=8YFLogxK
U2 - 10.1126/scisignal.2003199
DO - 10.1126/scisignal.2003199
M3 - Article
C2 - 23092893
AN - SCOPUS:84868159785
SN - 1945-0877
VL - 5
JO - Science Signaling
JF - Science Signaling
IS - 247
M1 - ra77
ER -
