Sun Y, Liu X, Ng-Eaton E, Lodish H F, Weinberg R A
Whitehead Institute for Biomedical Research, Nine Cambridge Center, Cambridge, MA 02142, USA.
Proc Natl Acad Sci U S A. 1999 Oct 26;96(22):12442-7. doi: 10.1073/pnas.96.22.12442.
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.
转化生长因子β（TGF-β）调节多种生理过程，包括生长抑制、分化和凋亡诱导。一些由TGF-β启动的信号通过Smad3传递；TGF-β与其受体结合会诱导Smad3磷酸化，然后Smad3迁移至细胞核，在细胞核中它作为转录因子发挥作用。我们在此描述了Smad3与核原癌基因蛋白SnoN的关联。SnoN的过表达会抑制Smad3的转录激活。TGF-β信号的激活会导致SnoN以及程度较轻的相关Ski蛋白快速降解，这种降解可能由细胞蛋白酶体介导。这些结果证明了TGF-β信号通路级联的存在，在TGF-β刺激下，该级联会导致拮抗TGF-β信号激活的原癌蛋白被破坏。
