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

Transforming growth factor beta (TGF-beta) regulates a variety of physiolog ic processes, including growth inhibition, differentiation, and induction o f apoptosis. Some TGF-beta-initiated signals are conveyed through Smad3; TC F-beta binding to its receptors induces phosphorylation of Smad3, which the n migrates to the nucleus where it functions as a transcription factor. We describe here the association of Smad3 with the nuclear protooncogene prote in SnoN, Overexpression of SnoN represses transcriptional activation by Sma d3. 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 l ikely mediated by cellular proteasomes. These results demonstrate the exist ence of a cascade of the TGF-beta signaling pathway, which, upon TGF-beta s timulation, reads to the destruction of protooncoproteins that antagonize t he activation of the TCF-beta signaling.