Vignais M L
IGM/CNRS UMR 5535, 1919, route de Mende, 34293 Montpellier Cedex 5.
Bull Cancer. 2000 Feb;87(2):135-7.
Ski and SnoN are two proto-oncogenes that, at high cellular concentrations, are associated with tumors. Up to now, apart the fact that SnoN and Ski were known to bind to DNA indirectly, very little was known about the mechanism which enables these factors to induce tumorigenesis. We know now that SnoN and Ski interact with the SMAD proteins which are mediators of TGFbeta signaling. These SMADs enable recruitment to target gene promoters of SnoN and Ski as well as the histone deacetylase activity which is associated with them. Whereas physiologic concentrations of SnoN and Ski allow a feedback regulation of TGFbeta signaling, deregulation of SnoN or Ski expression leads to total inhibition of TGFbeta signaling and of the tumor suppressors Smad2 and Smad4, which can explain the role of SnoN and Ski as oncogenes.
Ski和SnoN是两个原癌基因,在细胞内浓度较高时与肿瘤相关。到目前为止,除了已知SnoN和Ski间接结合DNA外,对于这些因子诱导肿瘤发生的机制知之甚少。我们现在知道,SnoN和Ski与SMAD蛋白相互作用,而SMAD蛋白是TGFβ信号传导的介质。这些SMAD蛋白能够募集SnoN和Ski至靶基因启动子以及与之相关的组蛋白脱乙酰酶活性。虽然生理浓度的SnoN和Ski可对TGFβ信号传导进行反馈调节,但SnoN或Ski表达失调会导致TGFβ信号传导以及肿瘤抑制因子Smad2和Smad4完全受到抑制,这可以解释SnoN和Ski作为癌基因的作用。