SUMO-1 modification activated GATA4-dependent cardiogenic gene activity
SUMO-1 modification activated GATA4-dependent cardiogenic gene activity
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DOI：
10.1074/jbc.m407494200
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发表时间：
2004-11-19
影响因子：
4.8
通讯作者：
Schwartz, RJ
中科院分区：
文献类型：
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作者：
Wang, J;Feng, XH;Schwartz, RJ
Sumoylation是一个重要的翻译后修饰过程，参与调节各种蛋白质的生物活性。 GATA4是一种富含心脏的双锌指转录因子，在调节心脏指定基因中起着至关重要的作用。在这里，我们证明了GATA4是由小型泛素样修饰剂1（SUMO-1）汇总的，这导致了增强的GATA4转录活性。我们进一步揭示了GATA4的赖氨酸366构成了主要的苏牛位点。将赖氨酸366转化为精氨酸366导致GATA4核占用减少，这表明SUMO修饰也可能调节GATA4核定位。在GATA4 sumoylation中，PIAS1用作E3连接酶，并通过其环手指域进行了正面调节的GATA4反式激活。在SUMO-1和/或PIAS1的存在下，GATA4触发了多能10T1/2成纤维细胞中心源基因的激活。 GATA4被确定为SUMO-1靶向转录因子，并与PIAS1一起被证明是心脏基因活性的有效调节剂。
Sumoylation, an important posttranslational modification process, is involved in regulating bioactivities of diverse proteins. GATA4, a cardiac-enriched dual zinc finger transcription factor, plays a critical role in regulating cardiac-specified genes. Here, we demonstrated that GATA4 is sumoylated by small ubiquitin-like modifier-1 (SUMO-1), which resulted in enhanced GATA4 transcriptional activity. We further revealed that lysine 366 of GATA4 constituted a major sumyolation site. Conversion of lysine 366 to arginine 366 resulted in reduced GATA4 nuclear occupation, suggesting that SUMO modification may also modulate GATA4 nuclear localization. In GATA4 sumoylation, PIAS1 served as an E3 ligase and positively modulated GATA4 transactivation via its RING finger domain. In the presence of SUMO-1 and/or PIAS1, GATA4 triggered the activation of cardiogenic genes in pluripotent 10T1/2 fibroblast. GATA4 was identified as a SUMO-1-targeted transcription factor and together with PIAS1 was shown to be a potent regulator of cardiac gene activity.