Lamouille Samy, Derynck Rik
Department of Cell and Tissue Biology, Programs in Cell Biology and Developmental Biology, University of California at San Francisco, San Francisco, CA, USA.
EMBO J. 2009 Nov 18;28(22):3459-60. doi: 10.1038/emboj.2009.311.
SnoN was first identified based on its homology with the proto-oncogene c-Ski, and has since been implicated as a promoter of oncogenic transformation and cancer progression. Consistent with a role as proto-oncogene, SnoN negatively regulates TGF-beta signalling, through its interactions with Smad complexes. Thus, SnoN inhibits the growth inhibitory effect of TGF-beta, which is considered as the basis for the tumour suppressor activity of TGF-beta signalling. In this issue of The EMBO Journal, Pan et al (2009) now demonstrate that SnoN also functions as a tumour suppressor, independently of its role in Smad signalling. The tumour suppressor role of SnoN results from its interaction with the promyelocytic leukaemia (PML) protein and the accumulation of SnoN in PML nuclear bodies, thus allowing SnoN to stabilize p53 and induce premature senescence.
SnoN最初是基于其与原癌基因c-Ski的同源性而被鉴定出来的，此后它被认为是致癌转化和癌症进展的促进因子。与作为原癌基因的作用一致，SnoN通过与Smad复合物相互作用，对转化生长因子-β（TGF-β）信号通路起负调控作用。因此，SnoN抑制了TGF-β的生长抑制作用，而这被认为是TGF-β信号通路具有肿瘤抑制活性的基础。在本期《EMBO杂志》中，Pan等人（2009年）现在证明，SnoN还具有肿瘤抑制作用，且与其在Smad信号通路中的作用无关。SnoN的肿瘤抑制作用源于它与早幼粒细胞白血病（PML）蛋白的相互作用以及SnoN在PML核体中的积累，从而使SnoN能够稳定p53并诱导细胞早衰。
