《自然》（Nature）雜志發(fā)表文章稱,，美國哈佛大學(xué)醫(yī)學(xué)院Dana-Farber癌癥研究所找到了一種物質(zhì),，能夠激活可殺死細胞的蛋白質(zhì)，這個發(fā)現(xiàn)有助于研發(fā)治療癌癥等疾病的新方法。
人體可以自動激活該蛋白質(zhì)BAX，殺死不需要的或有缺陷的細胞,，這一過程稱為“細胞凋亡(apoptosis)”，,。而哈佛大學(xué)的研究者認(rèn)為他們找到了激活“細胞凋亡”過程的方法,。
Loren Walensky博士說： “我們找到了能激活蛋白質(zhì)BAX的物質(zhì)，我們相信,，可以籍此研發(fā)可以打開或關(guān)閉人體細胞死亡程序的藥物,，實現(xiàn)治療目的。”
Walensky表示,，其團隊發(fā)現(xiàn)縮氨酸能恰到好處地激活“細胞凋亡”過程,。當(dāng)將縮氨酸放置到恰當(dāng)位置時,，蛋白質(zhì)BAX會在為細胞提供能量的線粒體膜上擊孔,，從而殺死細胞。
Walensky認(rèn)為,，可借助這種機制來研發(fā)藥物,。 Walensky是位于麻省劍橋的生物技術(shù)公司Aileron Therapeutics的創(chuàng)始人之一。（生物谷Bioon.com）
生物谷推薦原始出處：
Nature 455, 1076-1081 (23 October 2008) | doi:10.1038/nature07396
BAX activation is initiated at a novel interaction site
Evripidis Gavathiotis1,2,3,6, Motoshi Suzuki4,6, Marguerite L. Davis1,2,3, Kenneth Pitter1,2,3, Gregory H. Bird1,2,3, Samuel G. Katz1,2,3, Ho-Chou Tu5, Hyungjin Kim5, Emily H.-Y. Cheng5, Nico Tjandra4 & Loren D. Walensky1,2,3
1 Department of Pediatric Oncology and the Program in Cancer Chemical Biology, Dana-Farber Cancer Institute, 44 Binney Street, Boston, Massachusetts 02115, USA
2 Division of Hematology/Oncology, Children's Hospital Boston, 300 Longwood Avenue, Boston, Massachusetts 02115, USA
3 Department of Pediatrics, Harvard Medical School, Boston, Massachusetts 02115, USA
4 Laboratory of Molecular Biophysics, National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, Maryland 20892, USA
5 Departments of Internal Medicine and Pathology and Immunology, Washington University School of Medicine, Saint Louis, Missouri 63110, USA
6 These authors contributed equally to this work.
Abstract
BAX is a pro-apoptotic protein of the BCL-2 family that is stationed in the cytosol until activated by a diversity of stress stimuli to induce cell death. Anti-apoptotic proteins such as BCL-2 counteract BAX-mediated cell death. Although an interaction site that confers survival functionality has been defined for anti-apoptotic proteins, an activation site has not been identified for BAX, rendering its explicit trigger mechanism unknown. We previously developed stabilized -helix of BCL-2 domains (SAHBs) that directly initiate BAX-mediated mitochondrial apoptosis. Here we demonstrate by NMR analysis that BIM SAHB binds BAX at an interaction site that is distinct from the canonical binding groove characterized for anti-apoptotic proteins. The specificity of the human BIM-SAHB–BAX interaction is highlighted by point mutagenesis that disrupts functional activity, confirming that BAX activation is initiated at this novel structural location. Thus, we have now defined a BAX interaction site for direct activation, establishing a new target for therapeutic modulation of apoptosis.
