Oncogene and tumour suppressor: the two faces of SnoN.
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.
Lamouille
Samy
S
Department of Cell and Tissue Biology, Programs in Cell Biology and Developmental Biology, University of California at San Francisco, San Francisco, CA, USA.
Derynck
Rik
R
D000818:Animals; D002471:Cell Transformation, Neoplastic / Q000235:genetics; D016147:Genes, Tumor Suppressor / Q000502:physiology*; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000502:physiology*; D051379:Mice; D008954:Models, Biological; D009857:Oncogenes / Q000502:physiology*; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000502:physiology*; D015398:Signal Transduction / Q000235:genetics; D051785:Smad Proteins / Q000378:metabolism / Q000502:physiology; D014157:Transcription Factors / Q000235:genetics / Q000502:physiology; D016212:Transforming Growth Factor beta / Q000378:metabolism / Q000502:physiology
D047908:Intracellular Signaling Peptides and Proteins; C000715470:MAS1 protein, human; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins; C060615:SKIL protein, human; D051785:Smad Proteins; D014157:Transcription Factors; D016212:Transforming Growth Factor beta