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PMID: 8389697 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

c-fos transcriptional activation and repression correlate temporally with the phosphorylation status of TCF.

The EMBO journal ·Vol. 12 ·No. 6 ·1993-06-00 ·Pages 2377-87

Zinck R, Hipskind RA, Pingoud V, Nordheim A

Abstract

EGF-induction of human astrocytoma and A431 cells leads to c-fos transcriptional activation and then repression. This could be correlated with changes in the DNA binding characteristics of the c-fos regulatory protein ternary complex factor (TCF) present in nuclear extracts from these cells. Band shifts showed the appearance of induction-related slowly migrating protein-DNA complexes, detected as ternary complexes on the c-fos SRE using a truncated SRF molecule and by direct binding to the Drosophila E74 Ets-protein recognition sequence. By several criteria both types of complexes represented TCF. The appearance of the slow ternary and direct complexes correlated with c-fos transcriptional activation, and their disappearance coincided with the ensuing c-fos shut-off. Blocking c-fos transcriptional repression with the phosphatase inhibitor okadaic acid led to their continued presence. They were sensitive to protein phosphatase 2A but not 1 alpha, and similar slow complexes were formed by partially purified p62TCF phosphorylated by a copurifying kinase activity. Thus the phosphorylation state of TCF correlated strongly with c-fos promoter activity. Since ternary complex formation mediated by full-sized SRF was only slightly affected under comparable conditions, we propose a model for c-fos regulation involving modification of constitutively bound TCF.

Related Genes
c-fos
MeSH Terms
Cell Division/genetics DNA, Neoplasm/metabolism DNA-Binding Proteins/metabolism Ethers, Cyclic/pharmacology Genes, fos HeLa Cells Humans Okadaic Acid Phosphoprotein Phosphatases/metabolism Phosphorylation Promoter Regions, Genetic Protein Phosphatase 2 Transcription Factors/metabolism Transcriptional Activation Tumor Cells, Cultured
Chemicals
DNA, Neoplasm DNA-Binding Proteins Ethers, Cyclic Transcription Factors p62TCF protein, human Okadaic Acid Phosphoprotein Phosphatases Protein Phosphatase 2
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Zinck R
Hannover Medical School, Institute for Molecular Biology, Germany.
Hipskind R A
Pingoud V
Nordheim A
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Article Info
Journal
The EMBO journal
Abbr.
EMBO J
ISSN
0261-4189
Published
1993-06-00
Pages
2377-87
Language
English
Region
England
NLM ID
8208664
PMCID
PMC413468
Subset
IM
External Links
PubMed source PMC Full Text View journal details
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