Sumoylation regulates the transcriptional activity of MafA in pancreatic β cells

Chunli Shao, Melanie H. Cobb

Research output: Contribution to journalArticle

25 Citations (Scopus)

Abstract

MafA is a transcriptional regulator expressed primarily in pancreatic β 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, Lys32, blocks its sumoylation in β cells. Incubation of β 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 β cells or its ubiquitin-dependent degradation. This study suggests that modification of MafA by SUMO modulates gene transcription and thereby β cell function.

Original languageEnglish (US)
Pages (from-to)3117-3124
Number of pages8
JournalJournal of Biological Chemistry
Volume284
Issue number5
DOIs
StatePublished - Jan 30 2009

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Sumoylation
Genes
Ubiquitin
Glucose
Transcription
Gene expression
Hydrogen Peroxide
Binding Sites
Cells
Degradation
Gene Expression
Mutation

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology
  • Molecular Biology

Cite this

Sumoylation regulates the transcriptional activity of MafA in pancreatic β cells. / Shao, Chunli; Cobb, Melanie H.

In: Journal of Biological Chemistry, Vol. 284, No. 5, 30.01.2009, p. 3117-3124.

Research output: Contribution to journalArticle

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