Protein Inhibitor of Activated STAT Y (PIASy) Regulates Insulin Secretion by Interacting with LIM Homeodomain Transcription Factor Isl1.
Protein Inhibitor of Activated STAT Y (PIASy) Regulates Insulin Secretion by Interacting with LIM Homeodomain Transcription Factor Isl1.
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激活 STAT Y 的蛋白抑制剂 (PIASy) 通过与 LIM 同源域转录因子 Isl1 相互作用来调节胰岛素分泌。
DOI：
10.1038/srep39308
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发表时间：
2016-12-21
影响因子：
4.6
通讯作者：
Cui S
中科院分区：
文献类型：
--
作者：
Yan C;Yu C;Zhang D;Cui Y;Zhou J;Cui S
已知LIM同源结构域转录因子Isl1在所有胰腺内分泌细胞中都有高表达，并在调节胰腺发育和胰岛素分泌方面发挥作用。已发现Isl1突变与2型糖尿病有关，但Isl1调节胰岛素合成和分泌的机制仍需阐明。在本研究中，激活的STAT Y蛋白抑制因子(PIASy)被鉴定为一种新的Isl1与酵母双杂交系统相互作用的蛋白，并通过免疫共沉淀实验进一步证实了它与Isl1的相互作用。PIASy和Isl1在人、小鼠胰腺和NITβ细胞中共定位。此外，PIASy和Isl1通过激活胰岛素启动子，以剂量依赖的方式上调胰岛素基因的表达和胰岛素的分泌。在2型糖尿病db/db小鼠中，PIASy和Isl1的mRNA表达水平也升高。此外，我们的结果表明，PIASy和Isl1通过Isl1同源结构域和PIASy环结构域共同激活胰岛素启动子。这些数据表明，PIASy通过与Isl1相互作用来调节胰岛素的合成和分泌，为胰岛素的调节提供了新的视角，尽管详细的分子机制需要在未来的研究中得到澄清。
It is known that the LIM homeodomain transcription factor Isl1 is highly expressed in all pancreatic endocrine cells and functions in regulating pancreatic development and insulin secretion. The Isl1 mutation has been found to be associated with type 2 diabetes, but the mechanism responsible for Isl1 regulation of insulin synthesis and secretion still needs to be elucidated. In the present study, the protein inhibitor of activated STAT Y (PIASy) was identified as a novel Isl1-interacting protein with a yeast two-hybrid system, and its interaction with Isl1 was further confirmed by a co-immunoprecipitation experiment. PIASy and Isl1 colocalize in human and mouse pancreas and NIT beta cells. Furthermore, PIASy and Isl1 upregulate insulin gene expression and insulin secretion in a dose-dependent manner by activating the insulin promoter. PIASy and Isl1 mRNA expression levels were also increased in type 2 diabetic db/db mice. In addition, our results demonstrate that PIASy and Isl1 cooperate to activate the insulin promoter through the Isl1 homeodomain and PIASy ring domain. These data suggest that that PIASy regulates insulin synthesis and secretion by interacting with Isl1 and provide new insight into insulin regulation, although the detailed molecular mechanism needs to be clarified in future studies.
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影响因子：
5.4
作者：
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