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Molecular and Cellular Biology, January 2007, p. 622-632, Vol. 27, No. 2
0270-7306/07/$08.00+0     doi:10.1128/MCB.01160-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

Myocardin Sumoylation Transactivates Cardiogenic Genes in Pluripotent 10T1/2 Fibroblasts{triangledown}

Jun Wang,1,2 AnKang Li,1,2,3 ZhiGao Wang,4 XinHua Feng,1 Eric N. Olson,4 and Robert J. Schwartz1,2*

Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, Texas 77030,1 Institute of Bioscience and Technology, Texas A&M University Health Science Center, 2121 W. Holcombe Boulevard, Houston, Texas 77030,2 Graduate Program in Cardiovascular Sciences, Baylor College of Medicine, Houston, Texas 77030,3 Departments of Molecular Biology and Pathology, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, Texas 753904

Received 29 June 2006/ Returned for modification 24 July 2006/ Accepted 16 October 2006

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 {alpha}-actin and {alpha}-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.

* Corresponding author. Mailing address: The Institute of Biosciences and Technology, The Texas A&M University Health Science Center, 2121 W. Holcombe, Houston, TX 77030. Phone: (713) 677-7710. Fax: (713) 677-7725. E-mail: rschwartz{at}ibt.tamhsc.edu.

{triangledown} Published ahead of print on 13 November 2006.

Molecular and Cellular Biology, January 2007, p. 622-632, Vol. 27, No. 2
0270-7306/07/$08.00+0     doi:10.1128/MCB.01160-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.



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