Journal article
Histone deacetylase inhibitors synergize p300 autoacetylation that regulates its transactivation activity and complex formation
Cancer research (Chicago, Ill.), Vol.67(5), pp.2256-2264
01 Mar 2007
PMCID: PMC4526273
PMID: 17332356
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
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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Details
- Title
- Histone deacetylase inhibitors synergize p300 autoacetylation that regulates its transactivation activity and complex formation
- Creators
- Daniel P Stiehl - Cardeza Foundation for Hematologic Research, Department of Medicine, Thomas Jefferson University, Philadelphia, PennsylvaniaDonna M Fath - Cardeza Foundation for Hematologic Research, Department of Medicine, Thomas Jefferson University, Philadelphia, PennsylvaniaDongming Liang - Cellular Biology and Signaling Program, Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, PennsylvaniaYubao Jiang - Cellular Biology and Signaling Program, Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, PennsylvaniaNianli Sang - Cellular Biology and Signaling Program, Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, Pennsylvania
- Publication Details
- Cancer research (Chicago, Ill.), Vol.67(5), pp.2256-2264
- Publisher
- American Association for Cancer Research (AACR); United States
- Grant note
- K01 CA098809 / NCI NIH HHS CA 098809 / NCI NIH HHS
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Biology
- Identifiers
- 991014878320204721
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