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Molecular and Cellular Biology, August 2005, p. 6592-6602, Vol. 25, No. 15
0270-7306/05/$08.00+0     doi:10.1128/MCB.25.15.6592-6602.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

Akt Phosphorylation of p300 at Ser-1834 Is Essential for Its Histone Acetyltransferase and Transcriptional Activity{dagger}

Wei-Chien Huang and Ching-Chow Chen*

Department of Pharmacology, College of Medicine, National Taiwan University, Taipei 10018, Taiwan

Received 24 October 2004/ Returned for modification 20 December 2004/ Accepted 4 May 2005

The PI3K/Akt pathway plays a critical role in the regulation of gene expression induced by numerous stimuli. p300, a transcriptional coactivator, acts in concert with transcription factors to facilitate gene expression. Here, we show that Akt is activated and translocated to the nucleus in response to tumor necrosis factor alpha. Nuclear Akt associates with p300 and phosphorylates its Ser-1834 both in vivo and in vitro. The phosphorylation induces recruitment of p300 to the ICAM-1 promoter, leading to the acetylation of histones in chromatin and association with the basal transcriptional machinery RNA polymerase II. These two events facilitate ICAM-1 gene expression and are abolished by the p300 S1834A mutant, inhibitors of PI3K/Akt, or small interfering RNA of Akt. Histone acetylation is attributed to the Akt-enhanced intrinsic histone acetyltransferase (HAT) activity of p300 and its association with another HAT, p/CAF. Our study provides a new insight into the molecular mechanism by which Akt promotes the transcriptional potential of p300.

* Corresponding author. Mailing address: Department of Pharmacology, College of Medicine, National Taiwan University, No. 1 Jen-Ai Road, 1st Section, Taipei 10018, Taiwan. Phone: 886-2-23123456, ext. 8321. Fax: 886-2-23947833. E-mail: ccchen{at}ha.mc.ntu.edu.tw.

{dagger} Supplemental material for this article may be found at http://mcb.asm.org/.

Molecular and Cellular Biology, August 2005, p. 6592-6602, Vol. 25, No. 15
0022-538X/05/$08.00+0     doi:10.1128/MCB.25.15.6592-6602.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.



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