The E3 SUMO ligase PIASγ is a novel interaction partner regulating the activity of diabetes associated hepatocyte nuclear factor-1α.

作者: Alba Kaci , Magdalena Keindl , Marie H. Solheim , Pål R. Njølstad , Lise Bjørkhaug

DOI: 10.1038/S41598-018-29448-W

关键词: Hepatocyte nuclear factorsSUMO proteinHEK 293 cellsProtein inhibitor of activated STATTranscription factorCell biologyHNF1A GeneRegulation of gene expressionPlasma protein bindingBiology

摘要: The transcription factor hepatocyte nuclear factor-1α (HNF-1A) is involved in normal pancreas development and function. Rare variants the HNF1A gene can cause monogenic diabetes, while common confer type 2 diabetes risk. precise mechanisms for regulation of HNF-1A, including role function post-translational modifications, are still largely unknown. Here, we present first evidence HNF-1A being a substrate SUMOylation cellulo identify two lysine (K) residues (K205 K273) as sites. Overexpression protein inhibitor activated STAT (PIASγ) represses transcriptional activity dependent on simultaneous at K205 K273. Moreover, PIASγ novel interaction partner whose expression leads to translocation periphery. Thus, our findings support that the E3 SUMO ligase regulates with functional implications, representing new targets drug precision medicine diabetes.

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