Smad regulation in TGF-beta signal transduction
2001 (English)In: Journal of Cell Science, ISSN 0021-9533, E-ISSN 1477-9137, Vol. 114, no Pt 24, 4359-4369 p.Article, review/survey (Other academic) Published
Smad proteins transduce signals from transforming growth factor-beta (TGF-beta) superfamily ligands that regulate cell proliferation, differentiation and death through activation of receptor serine/threonine kinases. Phosphorylation of receptor-activated Smads (R-Smads) leads to formation of complexes with the common mediator Smad (Co-Smad), which are imported to the nucleus. Nuclear Smad oligomers bind to DNA and associate with transcription factors to regulate expression of target genes. Alternatively, nuclear R-Smads associate with ubiquitin ligases and promote degradation of transcriptional repressors, thus facilitating target gene regulation by TGF-beta. Smads themselves can also become ubiquitinated and are degraded by proteasomes. Finally, the inhibitory Smads (I-Smads) block phosphorylation of R-Smads by the receptors and promote ubiquitination and degradation of receptor complexes, thus inhibiting signalling.
Place, publisher, year, edition, pages
2001. Vol. 114, no Pt 24, 4359-4369 p.
Activin Receptors; Type I/*metabolism/physiology, Animals, DNA-Binding Proteins/physiology, Humans, Phosphoproteins/physiology, Receptor Protein-Tyrosine Kinases/*metabolism/physiology, Receptors; Transforming Growth Factor beta/*metabolism/physiology, Research Support; Non-U.S. Gov't, Signal Transduction/*physiology, Trans-Activators/physiology, Transforming Growth Factor beta/*physiology
Medical and Health Sciences
IdentifiersURN: urn:nbn:se:uu:diva-73330PubMedID: 11792802OAI: oai:DiVA.org:uu-73330DiVA: diva2:101240