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J. Biol. Chem., Vol. 279, Issue 53, 55626-55632, December 31, 2004

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Identification of a Novel Serum Response Factor Cofactor in Cardiac Gene Regulation^*

Xiaomin Zhang, Gohar Azhar, Ying Zhong, and Jeanne Y. Wei

From the Donald W. Reynolds Department of Geriatrics, University of Arkansas for Medical Sciences and Geriatric Research, Education, and Clinical Center (GRECC), Central Arkansas Veterans Healthcare System, Little Rock, Arkansas 72205

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.

Received for publication, May 27, 2004 , and in revised form, September 16, 2004.

The nucleotide sequence(s) reported in this paper has been submitted to the GenBank^TM/EBI Data Bank with accession number(s) AY611629 and AY611630.

^* This work was supported in part by Grants AG18388 and AG19946 from the Department of Health and Human Services, the Geriatric Research, Education, and Clinical Center (GRECC), and the Central Arkansas Veterans Healthcare System. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

To whom correspondence may be addressed: Donald W. Reynolds Dept. of Geriatrics, University of Arkansas for Medical Sciences, 4301 W. Markham #748, Little Rock, AR 72205. Fax: 501-686-5884; E-mail: zhangxiaomin{at}uams.edu.

To whom correspondence may be addressed: Donald W. Reynolds Dept. of Geriatrics, University of Arkansas for Medical Sciences, 4301 W. Markham #748, Little Rock, AR 72205. Fax: 501-686-5884; E-mail: jwei{at}uams.edu.

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