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Science. 1999 Oct 22;286(5440):771-4.

Negative feedback regulation of TGF-beta signaling by the SnoN oncoprotein.

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  • 1Life Sciences Division, Lawrence Berkeley National Laboratory, and Department of Molecular and Cell Biology, University of California, Berkeley, 229 Stanley Hall, Mail Code 3206, Berkeley, CA 94720, USA.

Abstract

Smad proteins mediate transforming growth factor-beta (TGF-beta) signaling to regulate cell growth and differentiation. The SnoN oncoprotein was found to interact with Smad2 and Smad4 and to repress their abilities to activate transcription through recruitment of the transcriptional corepressor N-CoR. Immediately after TGF-beta stimulation, SnoN is rapidly degraded by the nuclear accumulation of Smad3, allowing the activation of TGF-beta target genes. By 2 hours, TGF-beta induces a marked increase in SnoN expression, resulting in termination of Smad-mediated transactivation. Thus, SnoN maintains the repressed state of TGF-beta-responsive genes in the absence of ligand and participates in negative feedback regulation of TGF-beta signaling.

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PMID:
10531062
[PubMed - indexed for MEDLINE]
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