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

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 activat e transcription through recruitment of the transcriptional corepressor N-Co R, Immediately after TGF-beta stimulation, SnoN is rapidly degraded by the nuclear accumulation of Smad3, allowing the activation of TGF-beta target g enes. By 2 hours, TGF-beta induces a marked increase in SnoN expression, re sulting in termination of Smad-mediated transactivation. Thus, SnoN maintai ns the repressed state of TGF-beta-responsive genes in the absence of ligan d and participates in negative feedback regulation of TGF-beta signaling.