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PMID: 11027294 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Inhibition of p300 histone acetyltransferase by viral interferon regulatory factor.

Molecular and cellular biology ·Vol. 20 ·No. 21 ·2000-11-00 ·Pages 8254-63

Li M, Damania B, Alvarez X, Ogryzko V, Ozato K, Jung JU

Abstract

Kaposi's sarcoma-associated herpesvirus (KSHV) has been consistently identified in Kaposi's sarcomas, body cavity-based lymphomas, and some forms of Castleman's disease. The K9 open reading frame of KSHV encodes a viral interferon regulatory factor (vIRF) which functions as a repressor for cellular interferon-mediated signal transduction and as an oncogene to induce cell growth transformation. We demonstrate that KSHV vIRF directly interacts with cellular transcriptional coactivator p300 and displaces p300/CBP-associated factor from p300 complexes. This interaction inhibits the histone acetyltransferase activity of p300, resulting in drastic reduction of nucleosomal histone acetylation and alteration of chromatin structure. As a consequence, vIRF expression markedly alters cellular cytokine expression, which is regulated by acetylation of nucleosomal histones. These results demonstrate that KSHV vIRF interacts with and inhibits the p300 transcriptional coactivator to circumvent the host antiviral immune response and to induce a global alteration of cellular gene expression. These studies also illustrate how a cellular gene captured by a herpesvirus has evolved several functions that suit the needs of the virus.

MeSH Terms
3T3 Cells Acetylation Acetyltransferases/antagonists & inhibitors,metabolism Animals COS Cells Cell Cycle Cell Cycle Proteins/antagonists & inhibitors Cell Line Cell Separation Chromatin/metabolism Cytokines/metabolism DNA, Complementary/metabolism DNA-Binding Proteins/chemistry,metabolism Flow Cytometry Fluorescent Antibody Technique Genes, Reporter Herpesvirus 8, Human/metabolism Histone Acetyltransferases Histones/metabolism Insecta Interferon Regulatory Factors Mice Microscopy, Confocal Models, Genetic Mutagenesis, Site-Directed Nucleosomes/metabolism Open Reading Frames Plasmids/metabolism Promoter Regions, Genetic Saccharomyces cerevisiae Proteins Signal Transduction Transcription Factors/chemistry,metabolism Transcriptional Activation Transfection Viral Proteins p300-CBP Transcription Factors
Chemicals
Cell Cycle Proteins Chromatin Cytokines DNA, Complementary DNA-Binding Proteins Histones Interferon Regulatory Factors Nucleosomes Saccharomyces cerevisiae Proteins Transcription Factors Viral Proteins viral interferon regulatory factors Acetyltransferases Histone Acetyltransferases p300-CBP Transcription Factors p300-CBP-associated factor
Authors & Affiliations
6 authors, click to expand affiliations / ORCID
Li M
Department of Microbiology and Molecular Genetics, New England Regional Primate Research Center, Harvard Medical School, Southborough, Massachusetts 01772, USA.
Damania B
Alvarez X
Ogryzko V
Ozato K
Jung J U
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Article Info
Journal
Molecular and cellular biology
Abbr.
Mol Cell Biol
ISSN
0270-7306
DOI
10.1128/MCB.20.21.8254-8263.2000
Published
2000-11-00
Pages
8254-63
Language
English
Region
United States
NLM ID
8109087
PMCID
PMC86434
Subset
IM
Grants
NCI NIH HHS · CA82057 · United States
NCI NIH HHS · R01 CA082057 · United States
NCRR NIH HHS · P51 RR000168 · United States
NCRR NIH HHS · K26 RR000168 · United States
NCI NIH HHS · CA86841 · United States
NCI NIH HHS · CA31363 · United States
NCI NIH HHS · R01 CA031363 · United States
External Links
PubMed source DOI: 10.1128/MCB.20.21.8254-8263.2000 PMC Full Text View journal details
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