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【科普】特殊蛋白妨碍p53发挥作用
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）
更多阅读（英文）CHD8 suppresses p53-mediated apoptosis through histone H1 recruitment during early embryogenesis
Masaaki Nishiyama1,2, Kiyotaka Oshikawa1,2, Yu-ichi Tsukada1,2, Tadashi Nakagawa1,2, Shun-ichiro Iemura3, Tohru Natsume3, Yuhong Fan4,5, Akira Kikuchi6, Arthur I. Skoultchi4 & Keiichi I. Nakayama1,2
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AbstractThe 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.
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Department of Molecular and Cellular Biology, Medical Institute of Bioregulation, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, Fukuoka 812-8582, Japan.
CREST, Japan Science and Technology Agency (JST), Kawaguchi, Saitama 332-0012, Japan.
National Institute of Advanced Industrial Science and Technology (AIST), Biological Information Research Center (JBIRC), Kohtoh-ku, Tokyo 135-0064, Japan.
Department of Cell Biology, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, NY 10461, USA.
School of Biology and the Petit Institute for Bioengineering and Bioscience, Georgia Institute of Technology, IBB 2313, 315 Ferst Drive, Atlanta, GA 30332-0363, USA.
Department of Biochemistry, Graduate School of Biomedical Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima 734-8551, Japan. [标签:content1][标签:content2]
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作者:admin@医学,生命科学 2011-06-27 05:17
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