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Regulation of transforming growth factor‐β and bone morphogenetic protein signalling by transcriptional coactivator GCN5
Author(s) -
Kahata Kaoru,
Hayashi Makoto,
Asaka Masahiro,
Hellman Ulf,
Kitagawa Hirochika,
Yanagisawa Jun,
Kato Shigeaki,
Imamura Takeshi,
Miyazono Kohei
Publication year - 2004
Publication title -
genes to cells
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.912
H-Index - 115
eISSN - 1365-2443
pISSN - 1356-9597
DOI - 10.1111/j.1365-2443.2004.00706.x
Subject(s) - coactivator , smad , pcaf , biology , r smad , microbiology and biotechnology , nuclear receptor coactivator 3 , cancer research , transcription factor , transforming growth factor , genetics , gene , endoglin , stem cell , cd34
Smad proteins are intracellular signalling mediators of transforming growth factor‐β (TGF‐β) superfamily. In the nucleus, activated Smad complexes regulate transcriptional responses of the target genes in cooperation with transcriptional coactivators and corepressors. To identify new components of transcriptional complexes containing Smad proteins, we purified DNA‐binding proteins from human breast cancer MCF‐7 cell nuclear extract using a Smad‐binding DNA element as bait, and identified a coactivator GCN5 as a direct partner of activated Smad complexes. GCN5 is structurally similar to PCAF, which was previously identified as a coactivator for receptor‐regulated Smads (R‐Smads) for TGF‐β signalling pathways. GCN5 functions like PCAF, in that it binds to TGF‐β‐specific R‐Smads, and enhances transcriptional activity induced by TGF‐β. In addition, GCN5, but not PCAF, interacts with R‐Smads for bone morphogenetic protein (BMP) signalling pathways, and enhances BMP‐induced transcriptional activity, suggesting that GCN5 and PCAF have distinct physiological functions in vivo . Moreover, silencing of the GCN5 gene by RNA interference results in repression of transcriptional activities induced by TGF‐β. In conclusion we identified GCN5 as a Smad‐binding transcriptional coactivator which positively regulates both TGF‐β and BMP signalling pathways.