SnoN, an 80kD protein, is a member of ski family of nuclear proto-oncogenes involved in regulation of cellular transformation and differentiation. Primarily expressed in two isoforms, SnoN is localized in cytoplasm in normal tissues and non-tumorigenic primary epithelial cells. In cancer tissues or cells, SnoN is exclusively localized in the nucleus. It plays a vital role in inhibition of cell cycle arrest induced by TGF-â. Upon morphological differentiation or cell-cycle arrest, SnoN translocates into the nucleus, binds to Smad2, Smad3, and Smad4 on TGF- -responsive promoters and represses their ability to activate expression of TGF- target genes. It has also been found to mediate transcriptional repression of thyroid hormone receptor, Mad and pRb. Increased expression of SnoN has been detected in many human tumor cell lines suggesting a clinical significance.