Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P04626 (erbB-2)
 5,251 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Transforming growth factor beta (TGF-beta) regulates a variety of physiologic processes, including growth inhibition, differentiation, and induction of apoptosis. Some TGF-beta-initiated signals are conveyed through Smad3; TGF-beta binding to its receptors induces phosphorylation of Smad3, which then migrates to the nucleus where it functions as a transcription factor. We describe here the association of Smad3 with the nuclear protooncogene protein SnoN. Overexpression of SnoN represses transcriptional activation by Smad3. 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 likely mediated by cellular proteasomes. These results demonstrate the existence of a cascade of the TGF-beta signaling pathway, which, upon TGF-beta stimulation, leads to the destruction of protooncoproteins that antagonize the activation of the TGF-beta signaling.
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PMID:SnoN and Ski protooncoproteins are rapidly degraded in response to transforming growth factor beta signaling. 1053 41

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.
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PMID:Interaction of the Ski oncoprotein with Smad3 regulates TGF-beta signaling. 1054 82