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PMID: 9528808 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Differential transcriptional activation by human T-cell leukemia virus type 1 Tax mutants is mediated by distinct interactions with CREB binding protein and p300.

Molecular and cellular biology ·Vol. 18 ·No. 4 ·1998-04-00 ·Pages 2392-405

Bex F, Yin MJ, Burny A, Gaynor RB

Abstract

The human T-cell leukemia virus type 1 Tax protein transforms human T lymphocytes, which can lead to the development of adult T-cell leukemia. Tax transformation is related to its ability to activate gene expression via the ATF/CREB and the NF-kappaB pathways. Transcriptional activation of these pathways is mediated by the actions of the related coactivators CREB binding protein (CBP) and p300. In this study, immunocytochemistry and confocal microscopy were used to localize CBP and p300 in cells expressing wild-type Tax or Tax mutants that are able to selectively activate gene expression from either the NF-kappaB or ATF/CREB pathway. Wild-type Tax colocalized with both CBP and p300 in nuclear bodies which also contained ATF-1 and the RelA subunit of NF-kappaB. However, a Tax mutant that selectively activates gene expression from only the ATF/CREB pathway colocalized with CBP but not p300, while a Tax mutant that selectively activates gene expression from only the NF-kappaB pathway colocalized with p300 but not CBP. In vitro and in vivo protein interaction studies indicated that the integrity of two independent domains of Tax delineated by these mutants was involved in the direct interaction of Tax with either CBP or p300. These studies are consistent with a model in which activation of either the NF-kappaB or the ATF/CREB pathway by specific Tax mutants is mediated by distinct interactions with related coactivator proteins.

MeSH Terms
Activating Transcription Factor 1 Animals Binding Sites CREB-Binding Protein Cell Line Cell Nucleus/metabolism Cell Transformation, Viral Cricetinae Cyclic AMP Response Element Modulator DNA-Binding Proteins/metabolism Gene Expression Regulation, Viral Gene Products, tax/genetics,metabolism Human T-lymphotropic virus 1/genetics,physiology Humans Mutation NF-kappa B/metabolism Nuclear Proteins/metabolism Repressor Proteins Trans-Activators Transcription Factor RelA Transcription Factors/metabolism Transcription, Genetic Transcriptional Activation Tumor Cells, Cultured
Chemicals
Activating Transcription Factor 1 DNA-Binding Proteins Gene Products, tax NF-kappa B Nuclear Proteins Repressor Proteins Trans-Activators Transcription Factor RelA Transcription Factors Cyclic AMP Response Element Modulator CREB-Binding Protein CREBBP protein, human
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Bex F
Department of Medicine, University of Texas Southwestern Medical Center, Dallas 75235-8594, USA.
Yin M J
Burny A
Gaynor R B
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Article Info
Journal
Molecular and cellular biology
Abbr.
Mol Cell Biol
ISSN
0270-7306
DOI
10.1128/MCB.18.4.2392
Published
1998-04-00
Pages
2392-405
Language
English
Region
United States
NLM ID
8109087
PMCID
PMC121497
Subset
IM
External Links
PubMed source DOI: 10.1128/MCB.18.4.2392 PMC Full Text View journal details
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