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

Scientific Reports
Alba KaciIngvild Aukrust

Abstract

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

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Citations

Feb 6, 2020·The Journal of Clinical Endocrinology and Metabolism·Jana MalikovaLise Bjørkhaug

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Datasets Mentioned

BETA
BC104910.1

Methods Mentioned

BETA
immunoprecipitation
Electrophoretic mobility shift assay
confocal microscopy
co-immunoprecipitation
Assay
Protein Assay
transfection

Software Mentioned

SUMO
SUMOplot
GPS
Image Lab

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