Sumoylation regulates the transcriptional activity of MafA in pancreatic beta cells.
MafA is a transcriptional regulator expressed primarily in pancreatic beta cells. It binds to the RIPE3b/C1-binding site within the ins gene promoter, which plays a critical role in regulating ins gene expression in response to glucose. Here, we show that MafA is post-translationally modified by the small ubiquitin-related modifiers SUMO-1 and -2. Mutation of a single site in MafA, Lys(32), blocks its sumoylation in beta cells. Incubation of beta cells in low glucose (2 mm) or exposure to hydrogen peroxide increases sumoylation of endogenous MafA. Forced sumoylation of MafA results in reduced transcriptional activity toward the ins gene promoter and increased suppression of the CHOP-10 gene promoter. Sumoylation of MafA has no apparent effect on either its nuclear localization in beta cells or its ubiquitin-dependent degradation. This study suggests that modification of MafA by SUMO modulates gene transcription and thereby beta cell function.
Shao
Chunli
C
Department of Pharmacology, University of Texas Southwestern Medical Center, Dallas, Texas 75390-9041.
Cobb
Melanie H
MH
Department of Pharmacology, University of Texas Southwestern Medical Center, Dallas, Texas 75390-9041. Electronic address: Melanie.Cobb@UTSouthwestern.edu.
D000818:Animals; D001483:Base Sequence; D002460:Cell Line; D024202:Electrophoretic Mobility Shift Assay; D005455:Fluorescent Antibody Technique; D005947:Glucose / Q000378:metabolism; D007515:Islets of Langerhans / Q000166:cytology / Q000378:metabolism*; D037181:Lectins, C-Type / Q000502:physiology*; D051473:Maf Transcription Factors, Large / Q000502:physiology*; D008562:Membrane Glycoproteins / Q000502:physiology*; D051379:Mice; D009838:Oligodeoxyribonucleotides; D018384:Oxidative Stress; D051381:Rats; D025842:SUMO-1 Protein / Q000502:physiology*; D014158:Transcription, Genetic / Q000502:physiology*
C094696:Klrg1 protein, rat; D037181:Lectins, C-Type; D051473:Maf Transcription Factors, Large; C485160:Mafa protein, mouse; D008562:Membrane Glycoproteins; D009838:Oligodeoxyribonucleotides; D025842:SUMO-1 Protein; D005947:Glucose