Research Article

Cellular and Molecular Life Sciences CMLS

, Volume 61, Issue 13, pp 1675-1683

First online:

Role of Akt/protein kinase B in the activity of transcriptional coactivator p300

  • J. ChenAffiliated withOttawa Health Research Institute, University of Ottawa
  • , S. S. HalappanavarAffiliated withOttawa Health Research Institute, University of Ottawa
  • , J. R. St-GermainAffiliated withOttawa Health Research Institute, University of Ottawa
  • , B. K. TsangAffiliated withOttawa Health Research Institute, University of OttawaDepartment of Cellular and Molecular Medicine, University of OttawaDepartment of Obstetrics and Gynecology, University of Ottawa
  • , Q. LiAffiliated withOttawa Health Research Institute, University of OttawaDepartment of Cellular and Molecular Medicine, University of OttawaDepartment of Medicine, University of Ottawa Email author 

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Abstract

Akt/protein kinase B is a downstream target of the phosphatidylinositol 3-kinase (PI3K) pathway and plays a critical role in promotion of cell survival. The function of transcriptional coactivator p300 is required by many transcription factors to either activate or repress gene expression. Here, we show that induction of PI3K enhances the metabolic stability of endogenous p300 protein. On the other hand, repression of PI3K by LY294002 induces p300 degradation through the 26S proteasome pathway and impedes the transcriptional activity of the coactivator. In addition, Akt interacts with the coactivator and the activity of Akt is required to maintain the steady-state level of p300. Our study provides a new insight into the molecular mechanisms by which the critical concentration of p300 protein is regulated and suggests a role for Akt in control of various cellular activities through the transcriptional coactivator p300.

Akt protein kinase B PI3K p300 coactivator protein degradation proteasome cellular signaling