Negative feedback regulation of TGF-β signaling by the SnoN oncoprotein

Shannon L. Stroschein, Wei Wang, Sharleen Zhou, Qiang Zhou, Kunxin Luo

Research output: Contribution to journalArticlepeer-review

424 Scopus citations

Abstract

Smad proteins mediate transforming growth factor-β (TGF-β) 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-β stimulation, SnoN is rapidly degraded by the nuclear accumulation of Smad3, allowing the activation of TGF-β target genes. By 2 hours, TGF-β induces a marked increase in SnoN expression, resulting in termination of Smad-mediated transactivation. Thus, SnoN maintains the repressed state of TGF-β-responsive genes in the absence of ligand and participates in negative feedback regulation of TGF-β signaling.

Original languageEnglish (US)
Pages (from-to)771-774
Number of pages4
JournalScience
Volume286
Issue number5440
DOIs
StatePublished - Oct 22 1999

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