PIAS-family proteins negatively regulate Glis3 transactivation function through SUMO modification in pancreatic β cells.

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 transcrip

SUBMITTER: Hoard TM 

PROVIDER: S-EPMC6077130 | biostudies-literature | 2018 Jul

REPOSITORIES: biostudies-literature