The sno gene, which encodes a component of the histone deacetylase complex, acts as a tumor suppressor in mice

The Ski and Sno oncoproteins are components of a macromolecular complex con taining the co-repressor N-CoR/SMRT, mSin3 and histone deacetylase. This co mplex has been implicated in the transcriptional repression exerted by a nu mber of repressors including nuclear hormone receptors and Mad, Furthermore , Ski and Sno negatively regulate transforming growth factor-beta (TGF-beta ) signaling by recruiting this complex to Smads, Here we show that loss of one copy of sno increases susceptibility to tumorigenesis in mice. Mice lac king sno died at an early stage of embryogenesis, and sno was required for blastocyst formation. Heterozygous (sno(+/-)) mice developed spontaneous ly mphomas at a low frequency and showed an increased level of tumor formation relative to wildtype mice when challenged with a chemical carcinogen. sno( +/-) embryonic fibroblasts had an increased gen, sno proliferative capacity and the introduction of activated Ki-Pas into these cells resulted in neop lastic transformation, The B cells, T cells and embryonic fibroblasts of sn o(+/-) mice had a decreased sensitivity to apoptosis or cell cycle arrest. These findings demonstrate that sno acts as a tumor suppressor at least in some types of cells.