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SUMO modification negatively modulates the transcriptional activity of CREB-binding protein via the recruitment of Daxx

2005; National Academy of Sciences; Volume: 102; Issue: 47 Linguagem: Inglês

10.1073/pnas.0504460102

1091-6490

Hong-Yi Kuo, Che‐Chang Chang, Jen-Chong Jeng, Hui-Mei Hu, Ding-Yen Lin, Gerd G. Maul, Roland P.S. Kwok, Hsiu-Ming Shih,

Peptidase Inhibition and Analysis

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.