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

Abstract:

: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.

authors

Kuo HY,Chang CC,Jeng JC,Hu HM,Lin DY,Maul GG,Kwok RP,Shih HM

doi

10.1073/pnas.0504460102

keywords:

subject

Has Abstract

pub_date

2005-11-22 00:00:00

pages

16973-8

issue

47

eissn

0027-8424

issn

1091-6490

pii

0504460102

journal_volume

102

pub_type

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