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SUMO-1 modification activated GATA4-dependent cardiogenic gene activity
Jun Wang1, Xin-Hua Feng, Robert J Schwartz
1Center for Cardiovascular Development, Division of Cardiovascular Sciences, Department of Medicine, Baylor College of Medicine, Houston, Texas 77030, USA.
The Journal of Biological Chemistry
|September 1, 2004
Summary
Small ubiquitin-like modifier-1 (SUMO-1) enhances GATA4 transcription factor activity by sumoylation at lysine 366. This posttranslational modification, involving PIAS1 E3 ligase, promotes cardiac gene activation.
Area of Science:
- Molecular Biology
- Posttranslational Modifications
- Gene Regulation
Background:
- Sumoylation is a critical posttranslational modification regulating protein bioactivities.
- GATA4, a cardiac transcription factor, is essential for cardiac-specific gene regulation.
Purpose of the Study:
- To investigate the role of sumoylation in GATA4 function.
- To identify the specific sumoylation site on GATA4 and its impact on transcriptional activity and nuclear localization.
- To elucidate the involvement of E3 ligases in GATA4 sumoylation.
Main Methods:
- Demonstration of GATA4 sumoylation by SUMO-1.
- Identification of lysine 366 as a major sumoylation site.
- Assessment of the effect of lysine 366 to arginine 366 mutation on GATA4 nuclear occupation.
- Characterization of PIAS1 as an E3 ligase for GATA4.
- Analysis of GATA4-mediated cardiogenic gene activation in pluripotent cells.
Main Results:
- GATA4 is sumoylated by SUMO-1, enhancing its transcriptional activity.
- Lysine 366 is a primary sumoylation site on GATA4.
- Mutation of lysine 366 reduces GATA4 nuclear occupation, suggesting a role in nuclear localization.
- PIAS1 acts as an E3 ligase, positively modulating GATA4 transactivation via its RING finger domain.
- SUMO-1 and PIAS1 promote GATA4-induced activation of cardiac genes in 10T1/2 fibroblasts.
Conclusions:
- GATA4 is a SUMO-1-targeted transcription factor.
- Sumoylation of GATA4 by SUMO-1, facilitated by PIAS1, enhances cardiac gene activity.
- This modification pathway is a potent regulator of cardiac gene expression.