Sumoylation of CoREST modulates its function as a transcriptional repressor.
It is emerging that covalent modifications of many transcription factors and co-factors by the small ubiquitin-like modifier (SUMO) can have a key role in modulating their transcriptional regulation. As SUMO modification is often associated with transcriptional repression, we studied whether it was involved in modulating the repressive activity of CoREST. We showed that CoREST can be modified by SUMO-1 at lysine 294. PIASxbeta interacted with CoREST in vitro and in vivo, and functions as an E3-ligase to mediate its sumoylation. Furthermore, SENP1 mediated the desumoylation of CoREST. Interestingly, mutation of the CoREST sumoylation site compromised its ability as a corepressor. These results demonstrate that SUMO-1 modification modulates the transcriptional repression by CoREST and is needed for its full repressive activity.
Faculty of Pharmaceutical Sciences at Kagawa Campus, Tokushima Bunri University, 1314-1 Shido, Sanuki, Kagawa 769-2193, Japan.
Ayako
A
Muraoka
Atsuyo
A
Maeda
Norie
N
Nakahara
Midori
M
Yokota
Tamotsu
T
Nishida
Tokumi
T
Maruyama
Takayuki
T
Ohshima
D002460:Cell Line; D056970:Co-Repressor Proteins; D003546:Cysteine Endopeptidases; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D010450:Endopeptidases / Q000378:metabolism; D006801:Humans; D008239:Lysine / Q000235:genetics / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D050828:Protein Inhibitors of Activated STAT / Q000378:metabolism; D011499:Protein Processing, Post-Translational; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism*; D025842:SUMO-1 Protein / Q000378:metabolism*; D014158:Transcription, Genetic; D044767:Ubiquitin-Protein Ligases / Q000378:metabolism
D056970:Co-Repressor Proteins; D004268:DNA-Binding Proteins; D009419:Nerve Tissue Proteins; C501001:PIAS2 protein, human; D050828:Protein Inhibitors of Activated STAT; C121019:RCOR1 protein, human; D012097:Repressor Proteins; D025842:SUMO-1 Protein; C495501:SUMO1 protein, human; D044767:Ubiquitin-Protein Ligases; D010450:Endopeptidases; C404512:SENP1 protein, human; D003546:Cysteine Endopeptidases; D008239:Lysine