Myocardin sumoylation transactivates cardiogenic genes in pluripotent 10T1/2 fibroblasts

Jun Wang, AnKang Li, ZhiGao Wang, XinHua Feng, Eric N. Olson, Robert J. Schwartz

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Abstract

Myocardin, a serum response factor (SRF)-dependent cofactor, is a potent activator of smooth muscle gene activity but a poor activator of cardiogenic genes in pluripotent 10T1/2 fibroblasts. Posttranslational modification of GATA4, another myocardin cofactor, by sumoylation strongly activated cardiogenic gene activity. Here, we found that myocardin's activity was strongly enhanced by SUMO-1 via modification of a lysine residue primarily located at position 445 and that the conversion of this residue to arginine (K445R) impaired myocardin transactivation. PIAS1 was involved in governing myocardin activity via its E3 ligase activity that stimulated myocardin sumoylation on an atypical sumoylation site(s) and by its physical association with myocardin. Myocardin initiated the expression of cardiac muscle-specified genes, such as those encoding cardiac α-actin and α-myosin heavy chain, in an SRF-dependent manner in 10T1/2 fibroblasts, but only in the presence of coexpressed SUMO-1/PIAS1. Thus, SUMO modification acted as a molecular switch to promote myocardin's role in cardiogenic gene expression.

Original languageEnglish (US)
Pages (from-to)622-632
Number of pages11
JournalMolecular and Cellular Biology
Volume27
Issue number2
DOIs
StatePublished - Jan 2007

Fingerprint

Sumoylation
Fibroblasts
Genes
Serum Response Factor
Cardiac Myosins
myocardin
Ubiquitin-Protein Ligases
Myosin Heavy Chains
Post Translational Protein Processing
Transcriptional Activation
Lysine
Smooth Muscle
Arginine
Actins
Myocardium
Gene Expression

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cell Biology

Cite this

Myocardin sumoylation transactivates cardiogenic genes in pluripotent 10T1/2 fibroblasts. / Wang, Jun; Li, AnKang; Wang, ZhiGao; Feng, XinHua; Olson, Eric N.; Schwartz, Robert J.

In: Molecular and Cellular Biology, Vol. 27, No. 2, 01.2007, p. 622-632.

Research output: Contribution to journalArticle

Wang, Jun ; Li, AnKang ; Wang, ZhiGao ; Feng, XinHua ; Olson, Eric N. ; Schwartz, Robert J. / Myocardin sumoylation transactivates cardiogenic genes in pluripotent 10T1/2 fibroblasts. In: Molecular and Cellular Biology. 2007 ; Vol. 27, No. 2. pp. 622-632.
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