韓國(guó)首爾大學(xué)醫(yī)學(xué)院尹鴻德教授領(lǐng)導(dǎo)的研究團(tuán)隊(duì),，闡明了有關(guān)抑癌基因p53的活性調(diào)控機(jī)制的新理論,，被認(rèn)為開辟了新型癌癥治療藥物的新方向,。該項(xiàng)研究是在韓國(guó)教育科技部和韓國(guó)研究財(cái)團(tuán)的共同支援下完成的,。
作為研究目標(biāo)的p53基因是癌癥研究的核心方向,。研究人員發(fā)現(xiàn)，大約一半的癌癥患者體內(nèi)的p53基因發(fā)生了變異或者受到損傷,，p53基因正常功能的喪失被認(rèn)為同多種癌癥的發(fā)病直接相關(guān)。在正常情況下,，p53能夠啟動(dòng)損傷修復(fù)過程,，調(diào)控細(xì)胞周期。如果修復(fù)失敗,，p53還能啟動(dòng)細(xì)胞凋亡過程,，組織細(xì)胞突變向癌變轉(zhuǎn)化。
基因突變等因素將導(dǎo)致p53喪失活性,，使其失去對(duì)癌細(xì)胞增生的抑制能力,。但是相關(guān)研究始終未能在分析生物學(xué)的層面闡釋p53基因喪失活性的機(jī)制,。
尹鴻德領(lǐng)導(dǎo)的研究團(tuán)隊(duì)，利用實(shí)驗(yàn)鼠的胚胎干細(xì)胞和癌細(xì)胞解析了p53的生物學(xué)活性同鈣調(diào)磷酸酶結(jié)合蛋白1（CABIN1）的關(guān)系,。研究發(fā)現(xiàn),，為了迅速處理細(xì)胞損傷，在正常狀態(tài)下,，p53分布在基因附近但表現(xiàn)出低活性,。這是因?yàn)殁}調(diào)磷酸酶結(jié)合蛋白1同p53的結(jié)合使p53的功能受到抑制，但是細(xì)胞損傷發(fā)生后,，該蛋白能夠迅速同p53分離,，激發(fā)p53的活性，而且起到活性增強(qiáng)作用,。
據(jù)報(bào)道,，研究人員相信，這一成果被認(rèn)為開啟了p53研究的新天地,，為抗癌新藥的開發(fā)提供了新的方向,。（生物谷Bioon.com）
生物谷推薦原始出處：
Nature Structural & Molecular Biology 9 August 2009 | doi:10.1038/nsmb.1657
Cabin 1 restrains p53 activity on chromatin
Hyonchol Jang1, Soo-Youn Choi1, Eun-Jung Cho2 & Hong-Duk Youn1
Abstract
The tumor suppressor p53 has been proposed to bind target promoters upon genotoxic stress. However, recent evidence shows that p53 occupies some target promoters without such stress, suggesting that a negative regulator might render p53 transcriptionally inactive on these promoters. Here we show that calcineurin binding protein 1 (Cabin1) is a negative regulator of p53. Downregulation of Cabin1 induces activation of a subset of p53 target genes. Cabin1 physically interacts with p53 on these target promoters and represses p53 transcriptional activity in the absence of genotoxic stress, by regulating histone modification and p53 acetylation marks. Knockdown of Cabin1 retards cell growth and promotes cell death after DNA damage in a p53-dependent manner. Thus, Cabin1 inhibits p53 function on chromatin in the quiescent state; the presence of inactive p53 on some promoters might allow a prompt response upon DNA damage.
1 National Research Laboratory for Metabolic Checkpoint, Departments of Biomedical Sciences & Biochemistry and Molecular Biology, Cancer Research Institute, Seoul National University College of Medicine, Seoul, Republic of Korea.
2 National Research Laboratory for Chromatin Dynamics, College of Pharmacy, Sungkyunkwan University, Suwon, Republic of Korea.
