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

Direct link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf
Nuclear factor YY1 inhibits transforming growth factor beta- and bone morphogenetic protein-induced cell differentiation
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Ludwig Institute for Cancer Research.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Ludwig Institute for Cancer Research.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Ludwig Institute for Cancer Research.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Ludwig Institute for Cancer Research.
Show others and affiliations
2003 (English)In: Molecular and Cellular Biology, ISSN 0270-7306, E-ISSN 1098-5549, Vol. 23, no 13, 4494-4510 p.Article in journal (Refereed) Published
Abstract [en]

Smad proteins transduce transforming growth factor beta (TGF-beta) and bone morphogenetic protein (BMP) signals that regulate cell growth and differentiation. We have identified YY1, a transcription factor that positively or negatively regulates transcription of many genes, as a novel Smad-interacting protein. YY1 represses the induction of immediate-early genes to TGF-beta and BMP, such as the plasminogen activator inhibitor 1 gene (PAI-1) and the inhibitor of differentiation/inhibitor of DNA binding 1 gene (Id-1). YY1 inhibits binding of Smads to their cognate DNA elements in vitro and blocks Smad recruitment to the Smad-binding element-rich region of the PAI-1 promoter in vivo. YY1 interacts with the conserved N-terminal Mad homology 1 domain of Smad4 and to a lesser extent with Smad1, Smad2, and Smad3. The YY1 zinc finger domain mediates the association with Smads and is necessary for the repressive effect of YY1 on Smad transcriptional activity. Moreover, downregulation of endogenous YY1 by antisense and small interfering RNA strategies results in enhanced transcriptional responses to TGF-beta or BMP. Ectopic expression of YY1 inhibits, while knockdown of endogenous YY1 enhances, TGF-beta- and BMP-induced cell differentiation. In contrast, overexpression or knockdown of YY1 does not affect growth inhibition induced by TGF-beta or BMP. Accordingly, YY1 does not interfere with the regulation of immediate-early genes involved in the TGF-beta growth-inhibitory response, the cell cycle inhibitors p15 and p21, and the proto-oncogene c-myc. In conclusion, YY1 represses Smad transcriptional activities in a gene-specific manner and thus regulates cell differentiation induced by TGF-beta superfamily pathways.

Place, publisher, year, edition, pages
2003. Vol. 23, no 13, 4494-4510 p.
Keyword [en]
Actins/metabolism, Alkaline Phosphatase/metabolism, Animals, Blotting; Northern, Bone Morphogenetic Proteins/antagonists & inhibitors/*metabolism, COS Cells, Cell Differentiation, Cell Division, Cell Line, Cells; Cultured, Chromatin/metabolism, DNA/metabolism, DNA-Binding Proteins/metabolism/*physiology, Dose-Response Relationship; Drug, Glutathione Transferase/metabolism, Humans, Mice, Microscopy; Fluorescence, Plasmids/metabolism, Precipitin Tests, Protein Binding, Protein Structure; Tertiary, RNA; Small Interfering/metabolism, Research Support; Non-U.S. Gov't, Reverse Transcriptase Polymerase Chain Reaction, Thymidine/metabolism, Trans-Activators/metabolism, Transcription Factors/*physiology, Transcription; Genetic, Transforming Growth Factor beta/antagonists & inhibitors/*metabolism, Tumor Cells; Cultured
National Category
Medical and Health Sciences
Identifiers
URN: urn:nbn:se:uu:diva-73712DOI: 10.1128/MCB.23.13.4494-4510.2003PubMedID: 12808092OAI: oai:DiVA.org:uu-73712DiVA: diva2:101622
Available from: 2007-03-27 Created: 2007-03-27 Last updated: 2017-12-14Bibliographically 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=12808092&dopt=Citation

Authority records BETA

Pardali, Katerinaten Dijke, PeterHeldin, Carl-HenrikEricsson, JohanMoustakas, Aristidis

Search in DiVA

By author/editor
Pardali, Katerinaten Dijke, PeterHeldin, Carl-HenrikEricsson, JohanMoustakas, Aristidis
By organisation
Ludwig Institute for Cancer Research
In the same journal
Molecular and Cellular Biology
Medical and Health Sciences

Search outside of DiVA

GoogleGoogle Scholar

doi
pubmed
urn-nbn

Altmetric score

doi
pubmed
urn-nbn
Total: 604 hits
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf