期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：1999
卷号：96
期号：22
页码：12442-12447
DOI：10.1073/pnas.96.22.12442
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：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.
