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Histone deacetylase inhibitors synergize p300 autoacetylation that regulates its transactivation activity and complex formation
Journal article   Open access   Peer reviewed

Histone deacetylase inhibitors synergize p300 autoacetylation that regulates its transactivation activity and complex formation

Daniel P Stiehl, Donna M Fath, Dongming Liang, Yubao Jiang and Nianli Sang
Cancer research (Chicago, Ill.), v 67(5), pp 2256-2264
01 Mar 2007
DOI: https://doi.org/10.1158/0008-5472.CAN-06-3985
PMID: 17332356
Featured in Collection :   UN Sustainable Development Goals @ Drexel
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https://doi.org/10.1158/0008-5472.CAN-06-3985View
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Abstract

Protein Structure, Tertiary Amino Acid Sequence Catalytic Domain Humans Transcriptional Activation - drug effects Cell Cycle Proteins - metabolism Cells, Cultured Molecular Sequence Data Sequence Homology, Amino Acid Transcription Factors - metabolism p300-CBP Transcription Factors - metabolism Acetylation - drug effects Histone Acetyltransferases - metabolism Protein Binding Histone Deacetylase Inhibitors HeLa Cells p300-CBP Transcription Factors - chemistry Hydroxamic Acids - pharmacology
p300/cyclic AMP-responsive element binding protein-binding protein (CBP) are general coactivators for multiple transcription factors involved in various cellular processes. Several highly conserved domains of p300/CBP serve as interacting sites for transcription factors and regulatory proteins. Particularly, the intrinsic histone acetyltransferase (HAT) activity and transactivation domains (TAD) play essential roles for their coactivating function. Autoacetylation of p300/CBP is commonly observed in cell-free HAT assays and has been implicated in the regulation of their HAT activity. Here, we show that six lysine-rich regions in several highly conserved functional domains of p300 are targeted by p300HAT for acetylation in cell-free systems. We show that p300 is susceptible to acetylation in cultured tumor cells and that its acetylation status is affected by histone deacetylase inhibitor trichostatin A. We further show that either treatment with deacetylase inhibitors or coexpression of Gal4-p300HAT, which alone has no transactivation activity, stimulates the activity of the COOH-terminal TAD of p300 (p300C-TAD). We have defined the minimal p300C-TAD and show that it is sufficient to respond to deacetylase inhibitors and is a substrate for p300HAT. Finally, we show that acetylated p300 possesses enhanced ability to interact with p53. Taken together, our data suggest that acetylation regulates p300C-TAD and that acetylation of p300/CBP may contribute to the dynamic regulation of their complex formation with various interacting partners.

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Web of Science research areas
Oncology
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