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【Nature】特殊蛋白妨碍p53发挥作用
The chromodomain helicase DNA-binding (CHD) family of enzymes is thought to regulate gene expression, but their role in the regulation of specific genes has been unclear. Here we show that CHD8 is expressed at a high level during early embryogenesis and prevents apoptosis mediated by the tumour suppressor protein p53. CHD8 was found to bind to p53 and to suppress its transactivation activity. CHD8 promoted the association of p53 and histone H1, forming a trimeric complex on chromatin that was required for inhibition of p53-dependent transactivation and apoptosis. Depletion of CHD8 or histone H1 resulted in p53 activation and apoptosis. Furthermore, Chd8-/- mice died early during embryogenesis, manifesting widespread apoptosis, whereas deletion of p53 ameliorated this developmental arrest. These observations reveal a mode of p53 regulation mediated by CHD8, which may set a threshold for induction of apoptosis during early embryogenesis by counteracting p53 function through recruitment of histone H1.
据日本共同社报道，日本九州大学生体防御医学研究所教授中山敬一的研究小组发现了一种妨碍抗癌基因“p53”基因发挥作用的蛋白质，这种名为“CHD8”的蛋白质多存在于胎儿期的细胞中。
英国科学杂志《自然—细胞生物学》网络版19日登载了这一研究结果。
p53是具有代表性的“抗癌基因”，能在癌细胞等急速增殖过程中发生反应，促使癌细胞凋亡。专家认为阻碍其发挥作用后，癌细胞的增殖就等不到遏止。中山表示：“希望该发现能有助于探明癌症的发病机理。”
中山等人注意到在胎儿期，正常细胞和癌细胞一样迅速增殖。小白鼠实验结果显示，与CHD8结合在一起的p53无法引发细胞凋亡。专家们认为CHD8的作用在于使胎儿期活跃的细胞增殖不受阻碍。
中山表示：“如果能研制出防止CHD8和p53相结合的药物，将诞生抗癌新药。”（来源：中国新闻网）
（《自然—细胞生物学》（Nature Cell Biology ），doi:10.1038/ncb1831，Masaaki Nishiyama，Keiichi I. Nakayama） [标签:content1][标签:content2]
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作者:admin@医学,生命科学 2011-02-16 05:12
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