Document Type

Peer Reviewed/Refereed Publication

Publication Date

7-25-2018

Publication Title

Heliyon

Department

Biological Science

College/School

Jesse D. Jones College of Science, Engineering and Technology

Abstract

Gli-similar 3 (Glis3) is Krüppel-like transcription factor associated with the transcriptional regulation of insulin. Mutations within the Glis3 locus have been implicated in a number of pathologies including diabetes mellitus and hypothyroidism. Despite its clinical significance, little is known about the proteins and posttranslational modifications that regulate Glis3 transcriptional activity. In this report, we demonstrate that the SUMO-pathway associated proteins, PIASy and Ubc9 are capable of regulating Glis3 transactivation function through a SUMO-dependent mechanism. We present evidence that SUMOylation of Glis3 by PIAS-family proteins occurs at two conserved lysine residues within the Glis3 N-terminus and modification of Glis3 by SUMO dramatically inhibited insulin transcription. Finally, we provide evidence that Glis3 SUMOylation increases under conditions of chronically elevated glucose and correlates with decreased insulin transcription. Collectively, these results indicate that SUMOylation may serve as a mechanism to regulate Glis3 activity in β cells.

Creative Commons License

Creative Commons Attribution 4.0 License
This work is licensed under a Creative Commons Attribution 4.0 License.

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