title: Protein Inhibitor of Activated STAT Y (PIASy) Regulates Insulin Secretion by Interacting with LIM Homeodomain Transcription Factor Isl1.
abstract: 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.
authors.affiliation: State Key Laboratory of Agrobiotechnology, College of Biological Sciences, China Agricultural University, Beijing, China.
authors.forename: Chengzhi
authors.initials: C
authors.lastname: Yan
authors.affiliation: State Key Laboratory of Agrobiotechnology, College of Biological Sciences, China Agricultural University, Beijing, China.
authors.forename: Chulin
authors.initials: C
authors.lastname: Yu
authors.affiliation: State Key Laboratory of Agrobiotechnology, College of Biological Sciences, China Agricultural University, Beijing, China.
authors.forename: Di
authors.initials: D
authors.lastname: Zhang
authors.affiliation: Department of Pathology and Experimental Medicine, 306 Hospital of PLA, Beijing, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Cui
authors.affiliation: Department of Pathology and Experimental Medicine, 306 Hospital of PLA, Beijing, China.
authors.forename: Jinlian
authors.initials: J
authors.lastname: Zhou
authors.affiliation: State Key Laboratory of Agrobiotechnology, College of Biological Sciences, China Agricultural University, Beijing, China.
authors.forename: Sheng
authors.initials: S
authors.lastname: Cui
mesh_terms: D000818:Animals; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D006801:Humans; D047468:Immunoprecipitation; D007328:Insulin / Q000096:biosynthesis* / Q000378:metabolism*; D000078790:Insulin Secretion; D050417:Insulin-Secreting Cells / Q000502:physiology; D060850:LIM-Homeodomain Proteins / Q000378:metabolism*; D051379:Mice; D010179:Pancreas / Q000502:physiology; D000075223:Poly-ADP-Ribose Binding Proteins / Q000378:metabolism*; D011485:Protein Binding; D050828:Protein Inhibitors of Activated STAT / Q000378:metabolism*; D014157:Transcription Factors / Q000378:metabolism*; D020798:Two-Hybrid System Techniques
chemical_list: D007328:Insulin; D060850:LIM-Homeodomain Proteins; C485891:PIAS4 protein, human; D000075223:Poly-ADP-Ribose Binding Proteins; D050828:Protein Inhibitors of Activated STAT; D014157:Transcription Factors; C063843:insulin gene enhancer binding protein Isl-1