Title

PIASy and Ubc9 mediated SUMOylation enhances Glis3 transcriptional activity

List all Project Mentors & Advisor(s)

Dr. Gary ZeRuth

Presentation Format

Event

Abstract/Description

Gli-similar 3 (Glis3) is a Krüppel-like transcription factor that has been implicated in a number of human pathologies including polycystic kidney disease, Alzheimer’s disease, and cancer. Further, Glis3 has been shown to play a critical role in the regulation of insulin transcription and defective Glis3 signaling is associated with the development of both type 1 and type 2 diabetes. Despite its clinical significance, little is known about the proteins or posttranslational modifications that regulate Glis3 activity. In this study, we have identified two specific regions within the Glis3 protein that are targets for the small ubiquitin-like modifier (SUMO). We show that SUMOylation of Glis3 is mediated by proteins belonging to the Protein-Inhibitor of Activated STAT (PIAS) family as well as the E2 SUMO-conjugase, Ubc9. While the functional effect of SUMOylation on Glis3 remains unknown, we found that PIASy and Ubc9 co-expression significantly enhanced the transcriptional activity of Glis3, possibly by increasing Glis3 association with the ubiquitous co-activator, CREB Binding Protein (CBP). Collectively, these data identify SUMO as a novel regulator of Glis3 transcriptional activity and provide possible therapeutic targets for the treatment of Glis3-associated disease.

Location

Barkley Room, Curris Center

Start Date

April 2016

End Date

April 2016

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Apr 21st, 12:30 PM Apr 21st, 1:30 PM

PIASy and Ubc9 mediated SUMOylation enhances Glis3 transcriptional activity

Barkley Room, Curris Center

Gli-similar 3 (Glis3) is a Krüppel-like transcription factor that has been implicated in a number of human pathologies including polycystic kidney disease, Alzheimer’s disease, and cancer. Further, Glis3 has been shown to play a critical role in the regulation of insulin transcription and defective Glis3 signaling is associated with the development of both type 1 and type 2 diabetes. Despite its clinical significance, little is known about the proteins or posttranslational modifications that regulate Glis3 activity. In this study, we have identified two specific regions within the Glis3 protein that are targets for the small ubiquitin-like modifier (SUMO). We show that SUMOylation of Glis3 is mediated by proteins belonging to the Protein-Inhibitor of Activated STAT (PIAS) family as well as the E2 SUMO-conjugase, Ubc9. While the functional effect of SUMOylation on Glis3 remains unknown, we found that PIASy and Ubc9 co-expression significantly enhanced the transcriptional activity of Glis3, possibly by increasing Glis3 association with the ubiquitous co-activator, CREB Binding Protein (CBP). Collectively, these data identify SUMO as a novel regulator of Glis3 transcriptional activity and provide possible therapeutic targets for the treatment of Glis3-associated disease.