The sno gene, which encodes a component of the histone deacetylase complex, acts as a tumor suppressor in mice
The sno gene, which encodes a component of the histone deacetylase complex, acts as a tumor suppressor in mice
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DOI：
10.1093/emboj/19.10.2280
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发表时间：
2000-05-15
期刊：
影响因子：
11.4
通讯作者：
Ishii, S
中科院分区：
文献类型：
--
作者：
Shinagawa, T;Dong, HD;Ishii, S
Ski和Sno癌蛋白是含有辅阻遏物N-CoR/SMRT、mSin 3和组蛋白脱乙酰酶的大分子复合物的组分。该复合物与包括核激素受体和Mad在内的许多阻遏物所施加的转录抑制有关。此外，Ski和Sno通过将该复合物募集到Smads来负调节转化生长因子-β（TGF-β）信号传导。缺乏sno的小鼠在胚胎发育的早期就死亡，而sno是胚泡形成所必需的。杂合子（sno（+/-））小鼠自发性淋巴瘤的发生率较低，并且当用化学致癌物攻击时，相对于野生型小鼠，肿瘤形成水平增加。sno（+/-）小鼠胚胎成纤维细胞的增殖能力明显增强，Ki-Pas的导入可导致肿瘤性转化。sno（+/-）小鼠的B细胞、T细胞和胚胎成纤维细胞对凋亡或细胞周期阻滞的敏感性降低。这些发现表明，sno至少在某些类型的细胞中起肿瘤抑制作用。
The Ski and Sno oncoproteins are components of a macromolecular complex containing the co-repressor N-CoR/SMRT, mSin3 and histone deacetylase. This complex has been implicated in the transcriptional repression exerted by a number 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 lacking sno died at an early stage of embryogenesis, and sno was required for blastocyst formation. Heterozygous (sno(+/-)) mice developed spontaneous lymphomas 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 neoplastic transformation, The B cells, T cells and embryonic fibroblasts of sno(+/-) 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.