Identification of a novel serum response factor cofactor in cardiac gene regulation.
The transcription factor serum response factor (SRF) plays an important role in the regulation of a variety of cardiac genes during development and during adult aging. A novel SRF cofactor, herein called p49/STRAP, for SRF-dependent transcription regulation-associated protein, was recently identified in our laboratory. This protein interacted mainly with the transcriptional activation domain of the SRF protein and was found to bind to SRF or to the complex of SRF and another cofactor, such as myocardin or Nkx2.5. The expression of p49/STRAP affected the promoter activity of SRF target genes in a non-uniform manner. For example, p49 activated MLC2v and cardiac actin promoters when it was co-transfected with SRF, but it repressed atrial natriuretic factor promoter activity, which was strongly induced by myocardin. The p49/STRAP mRNA was observed to be highly expressed in fetal, adult, and senescent human hearts, and also in hearts of young adult and old mice, suggesting that p49/STRAP may be an important SRF cofactor in the transcriptional regulation of mammalian cardiac muscle genes throughout the life span.
Zhang
Xiaomin
X
Donald W. Reynolds Department of Geriatrics, University of Arkansas for Medical Sciences and Geriatric Research, 4301 W. Markham #748, Little Rock, AR 72205, USA.
Azhar
Gohar
G
Zhong
Ying
Y
Wei
Jeanne Y
JY
D000199:Actins / Q000235:genetics; D000375:Aging; D000595:Amino Acid Sequence; D000818:Animals; D009320:Atrial Natriuretic Factor / Q000378:metabolism; D015152:Blotting, Northern; D015153:Blotting, Western; D009202:Cardiomyopathies / Q000473:pathology; D018076:DNA, Complementary / Q000378:metabolism; D005786:Gene Expression Regulation; D005982:Glutathione Transferase / Q000378:metabolism; D000072576:Homeobox Protein Nkx-2.5; D018398:Homeodomain Proteins / Q000737:chemistry; D006801:Humans; D047468:Immunoprecipitation; D051379:Mice; D008856:Microscopy, Fluorescence; D008954:Models, Biological; D008969:Molecular Sequence Data; D009206:Myocardium / Q000378:metabolism* / Q000473:pathology; D041681:NIH 3T3 Cells; D009687:Nuclear Proteins / Q000737:chemistry; D010957:Plasmids / Q000378:metabolism; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D012333:RNA, Messenger / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D026362:Serum Response Factor / Q000737:chemistry* / Q000378:metabolism; D013997:Time Factors; D014018:Tissue Distribution; D015534:Trans-Activators / Q000737:chemistry; D014157:Transcription Factors / Q000737:chemistry* / Q000502:physiology*; D015533:Transcriptional Activation; D020798:Two-Hybrid System Techniques; D000099251:Myocardin
D000199:Actins; D009320:Atrial Natriuretic Factor; D018076:DNA, Complementary; D005982:Glutathione Transferase; D000072576:Homeobox Protein Nkx-2.5; D018398:Homeodomain Proteins; D009687:Nuclear Proteins; D012333:RNA, Messenger; D026362:Serum Response Factor; D015534:Trans-Activators; D014157:Transcription Factors; D000099251:Myocardin; C484469:Nkx2-5 protein, mouse; C496545:SRFBP1 protein, human; C496544:p49-STRAP protein, mouse