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

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

Research output: Contribution to journalArticle

85 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)16973-16978
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume102
Issue number47
DOIs
Publication statusPublished - Nov 22 2005
Externally publishedYes

Fingerprint

CREB-Binding Protein
Ubiquitin
Lysine
Histone Deacetylase 2
Sumoylation
Co-Repressor Proteins
Peptide Hydrolases
Transcription Factors
Mutation

Keywords

  • Histone deacetylase 2
  • Posttranslational modification
  • Protein-protein interaction
  • SENP2
  • Transcriptional repression

ASJC Scopus subject areas

  • Genetics
  • General

Cite this

SUMO modification negatively modulates the transcriptional activity of CREB-binding protein via the recruitment of Daxx. / Kuo, Hong Yi; Chang, Che Chang; Jeng, Jen Chong; Hu, Hui Mei; Lin, Ding Yen; Maul, Gerd G.; Kwok, Roland P S; Shih, Hsiu Ming.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 102, No. 47, 22.11.2005, p. 16973-16978.

Research output: Contribution to journalArticle

Kuo, Hong Yi ; Chang, Che Chang ; Jeng, Jen Chong ; Hu, Hui Mei ; Lin, Ding Yen ; Maul, Gerd G. ; Kwok, Roland P S ; Shih, Hsiu Ming. / SUMO modification negatively modulates the transcriptional activity of CREB-binding protein via the recruitment of Daxx. In: Proceedings of the National Academy of Sciences of the United States of America. 2005 ; Vol. 102, No. 47. pp. 16973-16978.
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