SUMO modification negatively modulates the transcriptional activity of CREB-binding protein via the recruitment of Daxx.
Small ubiquitin-like modifier (SUMO) modification is emerging as an important control in transcription regulation. Here, we show that CREB-binding protein (CBP), a versatile transcriptional coactivator for numerous transcription factors in response to diverse signaling events, can be modified by SUMO-1 at lysine residues 999, 1034, and 1057 both in vitro and in vivo. Mutation of the SUMO acceptor lysine residues either individually or in combination enhanced CBP transcriptional activity, and expression of a SUMO protease SENP2 potentiated the transcriptional activity of CBP wild-type but not its sumoylation mutant, indicating that SUMO modification negatively regulates CBP transcriptional activity. Furthermore, we demonstrated an interaction of SUMO-1-modified CBP with the transcriptional corepressor Daxx and an essential role of Daxx in mediating SUMO-dependent transcriptional regulation of CBP through histone deacetylase 2 recruitment. Together, our findings indicate that SUMO modification and subsequent recruitment of Daxx represent a previously undescribed mechanism in modulating CBP transcriptional potential.
Kuo
Hong-Yi
HY
Graduate Institute of Life Sciences, National Defense Medical Center, Taipei, Taiwan 11529, Republic of China.
Chang
Che-Chang
CC
Jeng
Jen-Chong
JC
Hu
Hui-Mei
HM
Lin
Ding-Yen
DY
Maul
Gerd G
GG
Kwok
Roland P S
RP
Shih
Hsiu-Ming
HM
D000818:Animals; D019556:COS Cells; D050882:CREB-Binding Protein / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D002352:Carrier Proteins / Q000378:metabolism* / Q000502:physiology; D002522:Chlorocebus aethiops; D056970:Co-Repressor Proteins; D015536:Down-Regulation / Q000502:physiology*; D006367:HeLa Cells; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism* / Q000502:physiology; D008239:Lysine / Q000235:genetics / Q000378:metabolism; D051379:Mice; D018832:Molecular Chaperones; D009687:Nuclear Proteins / Q000378:metabolism* / Q000502:physiology; D025842:SUMO-1 Protein / Q000502:physiology*; D014158:Transcription, Genetic / Q000502:physiology
D002352:Carrier Proteins; D056970:Co-Repressor Proteins; C491473:Daxx protein, mouse; D047908:Intracellular Signaling Peptides and Proteins; D018832:Molecular Chaperones; D009687:Nuclear Proteins; D025842:SUMO-1 Protein; D050882:CREB-Binding Protein; D008239:Lysine