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PMID: 10549282 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, Non-P.H.S. Research Support, U.S. Gov't, P.H.S.

Interaction of the Ski oncoprotein with Smad3 regulates TGF-beta signaling.

Molecular cell ·Vol. 4 ·No. 4 ·1999-10-00 ·Pages 499-509

Sun Y, Liu X, Eaton EN, Lane WS, Lodish HF, Weinberg RA

Abstract

TGF-beta treatment of cells induces a variety of physiologic responses, including growth inhibition, differentiation, and induction of apoptosis. TGF-beta induces phosphorylation and nuclear translocation of Smad3. We describe here the association of Smad3 with the nuclear protooncogene protein Ski in response to the activation of TGF-beta signaling. Association with Ski represses transcriptional activation by Smad3, and overexpression of Ski renders cells resistant to the growth-inhibitory effects of TGF-beta. The transcriptional repression as well as the growth resistance to TGF-beta by overexpression of Ski can be overcome by overexpression of Smad3. These results demonstrate that Ski is a novel component of the TGF-beta signaling pathway and shed light on the mechanism of action of the Ski oncoprotein.

MeSH Terms

Animals Carrier Proteins/genetics Cell Cycle Proteins Cell Division/genetics Cell Nucleus/metabolism Cells, Cultured Cyclin-Dependent Kinase Inhibitor p15 Cyclin-Dependent Kinase Inhibitor p16 DNA-Binding Proteins/genetics,metabolism Gene Expression Regulation Genes, myc/genetics Humans Mink Promoter Regions, Genetic Protein Binding Proto-Oncogene Proteins/genetics,metabolism Repressor Proteins/genetics Signal Transduction Smad3 Protein Trans-Activators/genetics,metabolism Transforming Growth Factor beta/pharmacology Tumor Suppressor Proteins

Chemicals

CDKN2B protein, human Carrier Proteins Cell Cycle Proteins Cyclin-Dependent Kinase Inhibitor p15 Cyclin-Dependent Kinase Inhibitor p16 DNA-Binding Proteins Proto-Oncogene Proteins Repressor Proteins SMAD3 protein, human Smad3 Protein Trans-Activators Transforming Growth Factor beta Tumor Suppressor Proteins SKI protein, human

Authors & Affiliations

6 authors, click to expand affiliations / ORCID

Sun Y

Whitehead Institute for Biomedical Research, Nine Cambridge Center, Massachusetts 02142, USA.

Liu X

Eaton E N

Lane W S

Lodish H F

Weinberg R A

Article Info

Journal

Molecular cell

Abbr.

Mol Cell

ISSN

1097-2765

DOI

10.1016/s1097-2765(00)80201-4

Published

1999-10-00

Pages

499-509

Language

English

Region

United States

NLM ID

9802571

Subset

Grants

NCI NIH HHS · CA63260 · United States

NCI NIH HHS · R35CA39826 · United States

External Links

PubMed source DOI: 10.1016/s1097-2765(00)80201-4 View journal details

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Interaction of the Ski oncoprotein with Smad3 regulates TGF-beta signaling.

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