SUMO-1 modification of MEF2A regulates its transcriptional activity.
Myocyte enhancer factor 2 (MEF2) transcription factors are crucial regulators controlling muscle-specific and growth factor-inducible genes. Numerous studies have reported that the activity of these transcription factors is tightly modulated by posttranslational modifications such as activation by specific phosphorylation as well as repression by class II histone deacetylases (HDACs). We hypothesized that MEF2 could also be regulated by covalent modification by SUMO-1, a reversible posttranslational modification which has been shown to regulate key proteins involved in cell proliferation, differentiation and tumor suppression. In this study, we demonstrate that MEF2A undergoes sumoylation primarily at a single lysine residue (K395) both in vitro and in vivo. We also show that the nuclear E3 ligase, PIAS1, promotes sumoylation of MEF2A. Mutation of lysine 395 to arginine abolishes MEF2A sumoylation and the sumoylation incompetent mutant protein has enhanced transcriptional activity compared to the wild type protein. Our results suggest that protein sumoylation could play a pivotal role in controlling MEF2 transcriptional activity.
Department of Chemistry and Biochemistry, University of Colorado-Boulder, Boulder, Colorado 80309, USA.
Cecilia
C
Riquelme
Kristen K B
KK
Barthel
Xuedong
X
Liu
D000595:Amino Acid Sequence; D000818:Animals; D002454:Cell Differentiation; D016384:Consensus Sequence; D008239:Lysine / Q000737:chemistry; D026161:MADS Domain Proteins / Q000235:genetics* / Q000378:metabolism*; D064326:MEF2 Transcription Factors; D051379:Mice; D008969:Molecular Sequence Data; D009154:Mutation; D018006:Myogenic Regulatory Factors / Q000235:genetics* / Q000378:metabolism*; D050828:Protein Inhibitors of Activated STAT / Q000378:metabolism*; D025842:SUMO-1 Protein / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D014158:Transcription, Genetic; D015533:Transcriptional Activation; D014162:Transfection; D044767:Ubiquitin-Protein Ligases / Q000378:metabolism
D026161:MADS Domain Proteins; D064326:MEF2 Transcription Factors; C578035:MEF2A protein, human; D018006:Myogenic Regulatory Factors; D050828:Protein Inhibitors of Activated STAT; D025842:SUMO-1 Protein; D044767:Ubiquitin-Protein Ligases; D008239:Lysine