Myocardin Sumoylation Transactivates Cardiogenic Genes in Pluripotent 10T1/2 Fibroblasts
- 1 January 2007
- journal article
- Published by Taylor & Francis in Molecular and Cellular Biology
- Vol. 27 (2), 622-632
- https://doi.org/10.1128/mcb.01160-06
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 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.Keywords
This publication has 59 references indexed in Scilit:
- The T-box factor TBX-2 and the SUMO conjugating enzyme UBC-9 are required for ABa-derived pharyngeal muscle in C. elegansDevelopmental Biology, 2006
- PIAS1 Activates the Expression of Smooth Muscle Cell Differentiation Marker Genes by Interacting with Serum Response Factor and Class I Basic Helix-Loop-Helix ProteinsMolecular and Cellular Biology, 2005
- Conditional Mutagenesis of the Murine Serum Response Factor Gene Blocks Cardiogenesis and the Transcription of Downstream Gene TargetsJournal of Biological Chemistry, 2005
- Activation of cardiac and smooth muscle-specific genes in primary human cells after forced expression of human myocardinCardiovascular Research, 2005
- Transcriptional activity of megakaryoblastic leukemia 1 (MKL1) is repressed by SUMO modificationGenes to Cells, 2005
- SUMOMolecular Cell, 2005
- Modification of the erythroid transcription factor GATA-1 by SUMO-1Proceedings of the National Academy of Sciences, 2004
- Regulation of Smad4 Sumoylation and Transforming Growth Factor-β Signaling by Protein Inhibitor of Activated STAT1Journal of Biological Chemistry, 2004
- PIASy-mediated repression of the androgen receptor is independent of sumoylationOncogene, 2004
- Molecular determinants of responses to myocardial ischemia/reperfusion injury: focus on hypoxia-inducible and heat shock factorsCardiovascular Research, 2004