Item Type: | Article |
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Title: | Independent and cooperative activation of chromosomal c-fos promoter by STAT3 |
Creators Name: | Yang, E., Lerner, L., 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 |
ISSN: | 0021-9258 |
Publisher: | American Society for Biochemistry and Molecular Biology |
Volume: | 278 |
Number: | 18 |
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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