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PMID: 10567539 Published · ppublish English Journal Article

PCAF interacts with tax and stimulates tax transactivation in a histone acetyltransferase-independent manner.

Molecular and cellular biology ·Vol. 19 ·No. 12 ·1999-12-00 ·Pages 8136-45

Jiang H, Lu H, Schiltz RL, Pise-Masison CA, Ogryzko VV, Nakatani Y, Brady JN

Abstract

Recent studies have shown that the p300/CREB binding protein (CBP)-associated factor (PCAF) is involved in transcriptional activation. PCAF activity has been shown strongly associated with histone acetyltransferase (HAT) activity. In this report, we present evidence for a HAT-independent transcription function that is activated in the presence of the human T-cell leukemia virus type 1 (HTLV-1) Tax protein. In vitro and in vivo GST-Tax pull-down and coimmunoprecipitation experiments demonstrate that there is a direct interaction between Tax and PCAF, independent of p300/CBP. PCAF can be recruited to the HTLV-1 Tax responsive element in the presence of Tax, and PCAF cooperates with Tax in vivo to activate transcription from the HTLV-1 LTR over 10-fold. Point mutations at Tax amino acid 318 (TaxS318A) or 319 to 320 (Tax M47), which have decreased or no activity on the HTLV-1 promoter, are defective for PCAF binding. Strikingly, the ability of PCAF to stimulate Tax transactivation is not solely dependent on the PCAF HAT domain. Two independent PCAF HAT mutants, which knock out acetyltransferase enzyme activity, activate Tax transactivation to approximately the same level as wild-type PCAF. In contrast, p300 stimulation of Tax transactivation is HAT dependent. These studies provide experimental evidence that PCAF contains a coactivator transcription function independent of the HAT activity on the viral long terminal repeat.

MeSH Terms
Acetyltransferases/metabolism Binding Sites CREB-Binding Protein Cell Cycle Proteins/metabolism DNA, Viral/metabolism Gene Expression Regulation, Viral Gene Products, tax/genetics,metabolism Histone Acetyltransferases Human T-lymphotropic virus 1/genetics Humans Nuclear Proteins/metabolism Recombinant Fusion Proteins/genetics,metabolism Response Elements Saccharomyces cerevisiae Proteins Terminal Repeat Sequences Trans-Activators/metabolism Transcription Factors Transcription, Genetic Transcriptional Activation p300-CBP Transcription Factors
Chemicals
Cell Cycle Proteins DNA, Viral Gene Products, tax Nuclear Proteins Recombinant Fusion Proteins Saccharomyces cerevisiae Proteins Trans-Activators Transcription Factors Acetyltransferases CREB-Binding Protein CREBBP protein, human Histone Acetyltransferases p300-CBP Transcription Factors p300-CBP-associated factor
Authors & Affiliations
7 authors, click to expand affiliations / ORCID
Jiang H
Virus Tumor Biology Section, Laboratory of Receptor Biology and Gene Expression, Division of Basic Sciences, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA.
Lu H
Schiltz R L
Pise-Masison C A
Ogryzko V V
Nakatani Y
Brady J N
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Article Info
Journal
Molecular and cellular biology
Abbr.
Mol Cell Biol
ISSN
0270-7306
DOI
10.1128/MCB.19.12.8136
Published
1999-12-00
Pages
8136-45
Language
English
Region
United States
NLM ID
8109087
PMCID
PMC84898
Subset
IM
Corrections
ErratumIn
-
External Links
PubMed source DOI: 10.1128/MCB.19.12.8136 PMC Full Text View journal details
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