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PMID: 2114014 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Unusual c-fos induction upon chromaffin PC12 differentiation by sodium butyrate: loss of fos autoregulatory function.

Nucleic acids research ·Vol. 18 ·No. 12 ·1990-06-25 ·Pages 3605-10

Naranjo JR, Mellström B, Auwerx J, Mollinedo F, Sassone-Corsi P

Abstract

Induction of PC12 pheochromocytoma cells neuronal differentiation upon treatment with nerve growth factor (NGF) is accompanied by a coupled stimulation of c-fos and c-jun oncogene transcription. We found that induction of c-fos and c-jun proto-oncogene mRNAs levels following the endocrine differentiation of PC12 cells by sodium butyrate is uncoupled. While c-fos mRNA level increased within minutes, the content of c-jun mRNA was significantly elevated only 24 hours after treatment. Continuous presence of sodium butyrate for 72 hours resulted in stable high levels of c-fos and c-jun mRNAs. Gene transcription of the other members of the jun family, jun B and jun D, was not significantly modified at any induction time. The early accumulation of c-fos mRNA was accompanied by increased levels of c-Fos protein. While the NGF-induced c-Fos protein migrates with an apparent homogeneous molecular weight of 62 kDa, the sodium butyrate-stimulated Fos protein is of heterogeneous lower molecular weight. The different gel mobility of the Fos immunoreactive bands induced by sodium butyrate and the sustained Fos mRNA levels after induction suggested that the sodium butyrate-induced c-Fos protein could be non-functional in the autoregulation of the c-fos gene. Gel shift analysis showed unimpaired capacity of the butyrate-induced c-Fos protein to participate in the formation of transcriptional complexes with the Jun/AP-1 protein. However, transfection experiments indicate that the sodium butyrate-induced c-Fos protein is not able to negatively trans-regulate the c-fos promoter.

MeSH Terms
Adrenal Gland Neoplasms Butyrates/pharmacology Butyric Acid Calmodulin/metabolism Cell Differentiation DNA-Binding Proteins/genetics,metabolism Gene Expression Regulation, Neoplastic Neurons/cytology Pheochromocytoma Proto-Oncogene Proteins/genetics Proto-Oncogene Proteins c-fos Proto-Oncogene Proteins c-jun Proto-Oncogenes RNA, Messenger/analysis Signal Transduction Transcription Factors/genetics,metabolism Tumor Cells, Cultured
Chemicals
Butyrates Calmodulin DNA-Binding Proteins Proto-Oncogene Proteins Proto-Oncogene Proteins c-fos Proto-Oncogene Proteins c-jun RNA, Messenger Transcription Factors Butyric Acid
Authors & Affiliations
5 authors, click to expand affiliations / ORCID
Naranjo J R
Instituto Cajal de Neurociencia, Consejo Superior Investigaciones Cientificas, Madrid, Spain.
Mellström B
Auwerx J
Mollinedo F
Sassone-Corsi P
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Article Info
Journal
Nucleic acids research
Abbr.
Nucleic Acids Res
ISSN
0305-1048
Published
1990-06-25
Pages
3605-10
Language
English
Region
England
NLM ID
0411011
PMCID
PMC331016
Subset
IM
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