日本九州大學(xué)生體防御醫(yī)學(xué)研究所教授中山敬一的研究小組發(fā)現(xiàn)了一種妨礙抗癌基因“p53”基因發(fā)揮作用的蛋白質(zhì),，這種名為“CHD8”的蛋白質(zhì)多存在于胎兒期的細(xì)胞中。
英國科學(xué)雜志《自然—細(xì)胞生物學(xué)》網(wǎng)絡(luò)版19日登載了這一研究結(jié)果。
p53是具有代表性的“抗癌基因”,，能在癌細(xì)胞等急速增殖過程中發(fā)生反應(yīng),，促使癌細(xì)胞凋亡,。專家認(rèn)為阻礙其發(fā)揮作用后,，癌細(xì)胞的增殖就等不到遏止。中山表示：“希望該發(fā)現(xiàn)能有助于探明癌癥的發(fā)病機(jī)理,。”
中山等人注意到在胎兒期,，正常細(xì)胞和癌細(xì)胞一樣迅速增殖。小白鼠實(shí)驗(yàn)結(jié)果顯示,，與CHD8結(jié)合在一起的p53無法引發(fā)細(xì)胞凋亡,。專家們認(rèn)為CHD8的作用在于使胎兒期活躍的細(xì)胞增殖不受阻礙。
中山表示：“如果能研制出防止CHD8和p53相結(jié)合的藥物,，將誕生抗癌新藥,。”（生物谷Bioon.com）
生物谷推薦原始出處：
Nature Cell Biology (18 Jan 2009), doi: 10.1038/ncb1831
CHD8 suppresses p53-mediated apoptosis through histone H1 recruitment during early embryogenesis
Masaaki Nishiyama, Kiyotaka Oshikawa, Yu-ichi Tsukada, Tadashi Nakagawa, Shun-ichiro Iemura, Tohru Natsume, Yuhong Fan, Akira Kikuchi, Arthur I. Skoultchi, Keiichi I. Nakayama
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.
1 Department of Molecular and Cellular Biology, Medical Institute of Bioregulation, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, Fukuoka 812-8582, Japan.
2 CREST, Japan Science and Technology Agency (JST), Kawaguchi, Saitama 332-0012, Japan.
3 National Institute of Advanced Industrial Science and Technology (AIST), Biological Information Research Center (JBIRC), Kohtoh-ku, Tokyo 135-0064, Japan.
4 Department of Cell Biology, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, NY 10461, USA.
5 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.
6 Department of Biochemistry, Graduate School of Biomedical Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima 734-8551, Japan.
