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PMID: 7588605 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

CBP-induced stimulation of c-Fos activity is abrogated by E1A.

The EMBO journal ·Vol. 14 ·No. 19 ·1995-10-02 ·Pages 4758-62

Bannister AJ, Kouzarides T

Abstract

The CBP protein stimulates transcription of cAMP-responsive genes by binding to the phosphorylated activation domain of the CREB transcription factor. Here we show that CBP stimulates transcription of Fos/Jun activity in F9 cells and that this response of mediated, at least partly, via c-Fos. We show that CBP binds c-Fos in a phosphorylation-independent manner in vitro, using a domain distinct from that required to bind CREB. When this CBP domain is linked to the activation domain of VP16 it can stimulate GAL4-Fos activity in vivo. The domain of CBP that binds c-Fos is also used to contact the E1A protein. We therefore asked whether the documented repression of AP1 activity by E1A is due to sequestration of CBP from c-Fos. We show that E1A 12S can repress c-Fos activation functions. The use of E1A mutants indicates that binding of CBP, but not RB, to E1A is essential for E1A-mediated repression. These data support a model whereby E1A can modulate AP1 activity by directly competing for the CBP co-activator protein.

MeSH Terms
Adenovirus E1A Proteins/metabolism,physiology Amino Acid Sequence CREB-Binding Protein Cell Line Herpes Simplex Virus Protein Vmw65/genetics Humans Molecular Sequence Data Nuclear Proteins/genetics,metabolism Proto-Oncogene Proteins c-fos/genetics,metabolism Proto-Oncogene Proteins c-jun/genetics,metabolism Recombinant Fusion Proteins/metabolism Trans-Activators Transcription Factors/genetics,metabolism Transcriptional Activation/physiology Transfection Tumor Cells, Cultured
Chemicals
Adenovirus E1A Proteins Herpes Simplex Virus Protein Vmw65 Nuclear Proteins Proto-Oncogene Proteins c-fos Proto-Oncogene Proteins c-jun Recombinant Fusion Proteins Trans-Activators Transcription Factors CREB-Binding Protein CREBBP protein, human
Authors & Affiliations
2 authors, click to expand affiliations / ORCID
Bannister A J
Wellcome/CRC Institute, University of Cambridge, UK.
Kouzarides T
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36 references, click to expand
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Article Info
Journal
The EMBO journal
Abbr.
EMBO J
ISSN
0261-4189
Published
1995-10-02
Pages
4758-62
Language
English
Region
England
NLM ID
8208664
PMCID
PMC394573
Subset
IM
Grants
Wellcome Trust · United Kingdom
External Links
PubMed source PMC Full Text View journal details
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