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Independent and cooperative activation of chromosomal c-fos promoter by STAT3

Item Type:Article
Title:Independent and cooperative activation of chromosomal c-fos promoter by STAT3
Creators Name:Yang, E. and Lerner, L. and Besser, D. and Darnell, J.E.
Abstract:The c-fos gene was one of the earliest vertebrate genes shown to be transcriptionally induced by growth factors. Intensive study of the promoter of c-fos (-325 to -80) by transient or permanent transfections of synthetic DNA constructs has repeatedly shown the importance of several sequence elements and the resident nuclear proteins that bind them (e.g. ternary complex factor/ELK1; serum response factor, cAMP response element-binding protein/amino-terminal fragment/AP-1). However these studies have left unanswered numerous questions about the role of these proteins in the regulation of the native chromosomal gene. In particular, the role of a site in this enhancer that binds STATs has been controversial. We present evidence here that STAT3 and not STAT1 accumulates on the chromosomal c-fos promoter and provides a boost to transcription without the activation of resident nuclear proteins through serine kinases. Also, when resident nuclear proteins such as ELK1 are activated to varying extents by mitogen-activated protein kinase pathways, STAT3 activation provides a 2-fold boost regardless of the final level of activated transcription. Thus the several proteins that interact with the c-fos enhancer apparently can act either in a cooperative or independent manner to achieve very different levels of transcription.
Keywords:DNA, DNA-Binding Proteins, fos Genes, Interleukin-6, Mitogen-Activated Protein Kinases, Genetic Promoter Regions, STAT1 Transcription Factor, STAT3 Transcription Factor, Trans-Activators
Source:Journal of Biological Chemistry
Publisher:American Society for Biochemistry and Molecular Biology
Page Range:15794-15799
Date:2 May 2003
Official Publication:https://doi.org/10.1074/jbc.M213073200
PubMed:View item in PubMed

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