Sumoylation Regulates the Transcriptional Activity of MafA in Pancreatic β Cells
Sumoylation Regulates the Transcriptional Activity of MafA in Pancreatic β Cells
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DOI：
10.1074/jbc.m806286200
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发表时间：
2009-01-30
影响因子：
4.8
通讯作者：
Cobb, Melanie H.
中科院分区：
文献类型：
--
作者：
Shao, Chunli;Cobb, Melanie H.
MafA是主要在胰腺β细胞中表达的转录调节因子。它与ins基因启动子内的RIPE 3b/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。在这里，我们表明MafA是后修饰的小泛素相关的修饰素SUMO-1和-2。MafA中单个位点的突变，即LyS（32），会阻止其在β细胞中的sumoylation。在低葡萄糖（2 mM）中孵育β细胞或暴露于过氧化氢增加内源MafA的类小泛素化。MafA的强制类小泛素化导致对ins基因启动子的转录活性降低和对CHOP-10基因启动子的抑制增加。MafA的SUMO化对其在β细胞中的核定位或其泛素依赖性降解没有明显影响。这项研究表明，通过SUMO修饰MafA调节基因转录，从而调节β细胞功能。
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.