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PMID: 10535941 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

SnoN and Ski protooncoproteins are rapidly degraded in response to transforming growth factor beta signaling.

Proceedings of the National Academy of Sciences of the United States of America ·Vol. 96 ·No. 22 ·1999-10-26 ·Pages 12442-7

Sun Y, Liu X, Ng-Eaton E, Lodish HF, Weinberg RA

Abstract

Transforming growth factor beta (TGF-beta) regulates a variety of physiologic processes, including growth inhibition, differentiation, and induction of apoptosis. Some TGF-beta-initiated signals are conveyed through Smad3; TGF-beta binding to its receptors induces phosphorylation of Smad3, which then migrates to the nucleus where it functions as a transcription factor. We describe here the association of Smad3 with the nuclear protooncogene protein SnoN. Overexpression of SnoN represses transcriptional activation by Smad3. Activation of TGF-beta signaling leads to rapid degradation of SnoN and, to a lesser extent, of the related Ski protein, and this degradation is likely mediated by cellular proteasomes. These results demonstrate the existence of a cascade of the TGF-beta signaling pathway, which, upon TGF-beta stimulation, leads to the destruction of protooncoproteins that antagonize the activation of the TGF-beta signaling.

MeSH Terms
Cell Line DNA-Binding Proteins/metabolism Humans Hydrolysis Intracellular Signaling Peptides and Proteins Ligands Plasminogen Activator Inhibitor 1/genetics Protein Binding Proto-Oncogene Proteins/metabolism Recombinant Proteins/metabolism Signal Transduction Smad3 Protein Trans-Activators/metabolism Transcription, Genetic Transforming Growth Factor beta/metabolism
Chemicals
DNA-Binding Proteins Intracellular Signaling Peptides and Proteins Ligands Plasminogen Activator Inhibitor 1 Proto-Oncogene Proteins Recombinant Proteins SKIL protein, human SMAD3 protein, human Smad3 Protein Trans-Activators Transforming Growth Factor beta SKI protein, human
Authors & Affiliations
5 authors, click to expand affiliations / ORCID
Sun Y
Whitehead Institute for Biomedical Research, Nine Cambridge Center, Cambridge, MA 02142, USA.
Liu X
Ng-Eaton E
Lodish H F
Weinberg R A
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Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
0027-8424
DOI
10.1073/pnas.96.22.12442
Published
1999-10-26
Pages
12442-7
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC22943
Subset
IM
Grants
NCI NIH HHS · R01CA63260 · United States
NCI NIH HHS · R35CA39826 · United States
External Links
PubMed source DOI: 10.1073/pnas.96.22.12442 PMC Full Text View journal details
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