2.50
Hdl Handle:
http://hdl.handle.net/10547/302087
Title:
Mechanisms of TGF-beta signaling in regulation of cell growth and differentiation
Authors:
Moustakas, Aristidis; Pardali, Katerina; Gaal, Annamaria; Heldin, Carl Henrik
Abstract:
Transforming growth factor beta (TGF-beta) is a secreted protein that regulates proliferation, differentiation and death of various cell types. All immune cell lineages, including B, T and dendritic cells as well as macrophages, secrete TGF-beta, which negatively regulates their proliferation, differentiation and activation by other cytokines. Thus, TGF-beta is a potent immunosuppressor and perturbation of TGF-beta signaling is linked to autoimmunity, inflammation and cancer. Regulation of cell proliferation and differentiation by TGF-beta is a topic of great basic and clinical importance. We summarize our work on the growth inhibitory pathway downstream of TGF-beta, which is triggered by receptor serine/threonine kinases at the cell surface and downstream effectors of the Smad family. Activated Smads regulate transcription of target genes, including cell cycle inhibitors such as p21, which mediate the anti-proliferative response and partially explain the tumor suppressive action of the TGF-beta pathway. We have described a molecular mechanism of regulation of the p21 gene by Smads and transcription factor Sp1. At late stages of tumor progression, TGF-beta promotes tumorigenesis via suppression of the immune system and changes in cell differentiation of epithelial tumor cells, a phenomenon termed epithelial to mesenchymal transdifferentiation (EMT). We review our work on the role of the Smad pathway in controlling EMT. In conclusion, the molecular pathways that describe the anti-proliferative and transdifferentiating effects of TGF-beta in epithelial cells have been uncovered to great molecular detail; a future challenge will be to test their generality in other systems, including the immune system.
Citation:
Moustakas, A., Pardali, K., Gal, A. and Heldin, C.H. (2002) 'Mechanisms of TGF-beta signaling in regulation of cell growth and differentiation', Immunology letters, 82(1-2),pp.85-91
Publisher:
Elsevier
Journal:
Immunology letters
Issue Date:
3-Jun-2002
URI:
http://hdl.handle.net/10547/302087
DOI:
10.1016/S0165-2478(02)00023-8
PubMed ID:
12008039
Additional Links:
http://www.ncbi.nlm.nih.gov/pubmed/12008039; http://www.sciencedirect.com/science/article/pii/S0165247802000238
Type:
Article
Language:
en
ISSN:
0165-2478
Appears in Collections:
Cell and Cryobiology Research Group

Full metadata record

DC FieldValue Language
dc.contributor.authorMoustakas, Aristidisen_GB
dc.contributor.authorPardali, Katerinaen_GB
dc.contributor.authorGaal, Annamariaen_GB
dc.contributor.authorHeldin, Carl Henriken_GB
dc.date.accessioned2013-09-23T11:32:00Zen
dc.date.available2013-09-23T11:32:00Zen
dc.date.issued2002-06-03en
dc.identifier.citationMoustakas, A., Pardali, K., Gal, A. and Heldin, C.H. (2002) 'Mechanisms of TGF-beta signaling in regulation of cell growth and differentiation', Immunology letters, 82(1-2),pp.85-91en_GB
dc.identifier.issn0165-2478en
dc.identifier.pmid12008039en
dc.identifier.doi10.1016/S0165-2478(02)00023-8en
dc.identifier.urihttp://hdl.handle.net/10547/302087en
dc.description.abstractTransforming growth factor beta (TGF-beta) is a secreted protein that regulates proliferation, differentiation and death of various cell types. All immune cell lineages, including B, T and dendritic cells as well as macrophages, secrete TGF-beta, which negatively regulates their proliferation, differentiation and activation by other cytokines. Thus, TGF-beta is a potent immunosuppressor and perturbation of TGF-beta signaling is linked to autoimmunity, inflammation and cancer. Regulation of cell proliferation and differentiation by TGF-beta is a topic of great basic and clinical importance. We summarize our work on the growth inhibitory pathway downstream of TGF-beta, which is triggered by receptor serine/threonine kinases at the cell surface and downstream effectors of the Smad family. Activated Smads regulate transcription of target genes, including cell cycle inhibitors such as p21, which mediate the anti-proliferative response and partially explain the tumor suppressive action of the TGF-beta pathway. We have described a molecular mechanism of regulation of the p21 gene by Smads and transcription factor Sp1. At late stages of tumor progression, TGF-beta promotes tumorigenesis via suppression of the immune system and changes in cell differentiation of epithelial tumor cells, a phenomenon termed epithelial to mesenchymal transdifferentiation (EMT). We review our work on the role of the Smad pathway in controlling EMT. In conclusion, the molecular pathways that describe the anti-proliferative and transdifferentiating effects of TGF-beta in epithelial cells have been uncovered to great molecular detail; a future challenge will be to test their generality in other systems, including the immune system.en_GB
dc.language.isoenen
dc.publisherElsevieren_GB
dc.relation.urlhttp://www.ncbi.nlm.nih.gov/pubmed/12008039en_GB
dc.relation.urlhttp://www.sciencedirect.com/science/article/pii/S0165247802000238en_GB
dc.subjectcell cycleen_GB
dc.subjectSmaden_GB
dc.subjecttransforming growth factor βen_GB
dc.subject.meshCell Differentiationen
dc.subject.meshCell Divisionen
dc.subject.meshCyclin-Dependent Kinase Inhibitor p21en
dc.subject.meshCyclinsen
dc.subject.meshEpithelial Cellsen
dc.subject.meshImmune Systemen
dc.subject.meshMesodermen
dc.subject.meshModels, Biologicalen
dc.subject.meshNeoplasmsen
dc.subject.meshSignal Transductionen
dc.subject.meshTransforming Growth Factor betaen
dc.titleMechanisms of TGF-beta signaling in regulation of cell growth and differentiationen
dc.typeArticleen
dc.identifier.journalImmunology lettersen_GB

Related articles on PubMed

All Items in UOBREP are protected by copyright, with all rights reserved, unless otherwise indicated.