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PMID: 7957108 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Serum-regulated transcription by serum response factor (SRF): a novel role for the DNA binding domain.

The EMBO journal ·Vol. 13 ·No. 22 ·1994-11-15 ·Pages 5421-32

Hill CS, Wynne J, Treisman R

Abstract

The transcription factors Serum Response Factor (SRF) and Ternary Complex Factor (TCF) form a ternary complex at the c-fos Serum Response Element (SRE). We show that in NIH3T3 cells TCF binding is required for regulated transcription in response to stimulation by phorbol myristate acetate (PMA), but not by whole serum. We constructed a novel transcriptionally inactive SRE variant whose serum-regulated activity can be partially restored by overexpression of SRF in the absence of bound TCF. Activation by SRF does not require the SRF N-terminal phosphorylation sites, but is potentiated 2- to 3-fold by the SRF C-terminal activation domain. Mutations in the SRF DNA binding domain, which do not affect the ability of SRF to bind DNA, abolish its ability to mediate TCF-independent serum-regulated activation and reduce activation by the SRF/TCF(Elk-1) ternary complex. Efficient activation requires that SRF be targeted to DNA via its own DNA binding domain.

MeSH Terms
3T3 Cells Animals Base Sequence Binding Sites Blood Physiological Phenomena DNA/genetics,metabolism DNA-Binding Proteins/physiology Gene Expression Regulation/drug effects Genes, fos HeLa Cells Humans Mice Molecular Sequence Data Nuclear Proteins/physiology Proto-Oncogene Proteins Recombinant Fusion Proteins/metabolism Regulatory Sequences, Nucleic Acid Retroviridae Proteins, Oncogenic/metabolism Serum Response Factor Tetradecanoylphorbol Acetate/pharmacology Transcription Factors Transcription, Genetic/drug effects ets-Domain Protein Elk-1
Chemicals
DNA-Binding Proteins Nuclear Proteins Proto-Oncogene Proteins Recombinant Fusion Proteins Retroviridae Proteins, Oncogenic Serum Response Factor Transcription Factors ets-Domain Protein Elk-1 p62TCF protein, human p62TCF protein, mouse DNA Tetradecanoylphorbol Acetate
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Hill C S
Transcription Laboratory, Imperial Cancer Research Fund, London, UK.
Wynne J
Treisman R
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Article Info
Journal
The EMBO journal
Abbr.
EMBO J
ISSN
0261-4189
Published
1994-11-15
Pages
5421-32
Language
English
Region
England
NLM ID
8208664
PMCID
PMC395499
Subset
IM
External Links
PubMed source PMC Full Text View journal details
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