Shao Chunli, Cobb Melanie H
Department of Pharmacology, University of Texas Southwestern Medical Center, Dallas, Texas 75390-9041.
Department of Pharmacology, University of Texas Southwestern Medical Center, Dallas, Texas 75390-9041.
J Biol Chem. 2009 Jan 30;284(5):3117-3124. doi: 10.1074/jbc.M806286200. Epub 2008 Nov 22.
MafA is a transcriptional regulator expressed primarily in pancreatic beta cells. It binds to the RIPE3b/C1-binding site within the ins gene promoter, which plays a critical role in regulating ins gene expression in response to glucose. Here, we show that MafA is post-translationally modified by the small ubiquitin-related modifiers SUMO-1 and -2. Mutation of a single site in MafA, Lys(32), blocks its sumoylation in beta cells. Incubation of beta cells in low glucose (2 mm) or exposure to hydrogen peroxide increases sumoylation of endogenous MafA. Forced sumoylation of MafA results in reduced transcriptional activity toward the ins gene promoter and increased suppression of the CHOP-10 gene promoter. Sumoylation of MafA has no apparent effect on either its nuclear localization in beta cells or its ubiquitin-dependent degradation. This study suggests that modification of MafA by SUMO modulates gene transcription and thereby beta cell function.
MafA是一种主要在胰腺β细胞中表达的转录调节因子。它与胰岛素（ins）基因启动子内的RIPE3b/C1结合位点结合，该位点在响应葡萄糖调节ins基因表达中起关键作用。在此，我们表明MafA会被小泛素相关修饰物SUMO-1和-2进行翻译后修饰。MafA中单个位点赖氨酸（Lys）32的突变会阻止其在β细胞中的SUMO化。将β细胞置于低葡萄糖（2 mM）环境中孵育或暴露于过氧化氢会增加内源性MafA的SUMO化。MafA的强制SUMO化会导致其对ins基因启动子的转录活性降低，以及对CHOP-10基因启动子的抑制作用增强。MafA的SUMO化对其在β细胞中的核定位或其泛素依赖性降解均无明显影响。这项研究表明，SUMO对MafA的修饰可调节基因转录，进而调节β细胞功能。
