TY - JOUR
T1 - Sumoylation regulates the transcriptional activity of MafA in pancreatic β cells
AU - Shao, Chunli
AU - Cobb, Melanie H.
PY - 2009/1/30
Y1 - 2009/1/30
N2 - 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.
AB - 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.
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U2 - 10.1074/jbc.M806286200
DO - 10.1074/jbc.M806286200
M3 - Article
C2 - 19029092
AN - SCOPUS:59149101860
SN - 0021-9258
VL - 284
SP - 3117
EP - 3124
JO - Journal of Biological Chemistry
JF - Journal of Biological Chemistry
IS - 5
ER -