uu.seUppsala University Publications
Change search
ReferencesLink to record
Permanent link

Direct link
Regulation of transforming growth factor-beta and bone morphogenetic protein signalling by transcriptional coactivator GCN5
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Ludwig Institute for Cancer Research.
Show others and affiliations
2004 (English)In: Genes to Cells, ISSN 1356-9597, E-ISSN 1365-2443, Vol. 9, no 2, 143-151 p.Article in journal (Refereed) Published
Abstract [en]

Smad proteins are intracellular signalling mediators of transforming growth factor-beta (TGF-beta) 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-beta signalling pathways. GCN5 functions like PCAF, in that it binds to TGF-beta-specific R-Smads, and enhances transcriptional activity induced by TGF-beta. 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-beta. In conclusion we identified GCN5 as a Smad-binding transcriptional coactivator which positively regulates both TGF-beta and BMP signalling pathways.

Place, publisher, year, edition, pages
2004. Vol. 9, no 2, 143-151 p.
Keyword [en]
Acetyltransferases/metabolism, Animals, Binding Sites, Bone Morphogenetic Proteins/*physiology, Breast Neoplasms/metabolism, Cell Extracts, Cell Line, Cloning; Molecular, DNA-Binding Proteins/metabolism, Humans, Plasminogen Activator Inhibitor 1/genetics, Precipitin Tests, Promoter Regions (Genetics)/genetics/physiology, Receptors; Growth Factor/genetics/metabolism, Regulatory Sequences; Nucleic Acid/genetics/physiology, Research Support; Non-U.S. Gov't, Signal Transduction, Trans-Activators/genetics/metabolism/*physiology, Transforming Growth Factor beta/genetics/metabolism/*physiology, Up-Regulation/genetics/physiology
National Category
Medical and Health Sciences
URN: urn:nbn:se:uu:diva-72988DOI: 10.1111/j.1365-2443.2004.00706.xPubMedID: 15009097OAI: oai:DiVA.org:uu-72988DiVA: diva2:100899
Available from: 2005-05-31 Created: 2005-05-31 Last updated: 2013-11-01Bibliographically approved

Open Access in DiVA

No full text

Other links

Publisher's full textPubMedhttp://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Retrieve&list_uids=15009097&dopt=Citation

Search in DiVA

By author/editor
Hellman, UlfMiyazono, Kohei
By organisation
Ludwig Institute for Cancer Research
In the same journal
Genes to Cells
Medical and Health Sciences

Search outside of DiVA

GoogleGoogle Scholar
The number of downloads is the sum of all downloads of full texts. It may include eg previous versions that are now no longer available

Altmetric score

Total: 201 hits
ReferencesLink to record
Permanent link

Direct link