《自然》（Nature）杂志发表文章称，美国哈佛大学医学院Dana-Farber癌症研究所找到了一种物质，能够激活可杀死细胞的蛋白质，这个发现有助于研发治疗癌症等疾病的新方法。
人体可以自动激活该蛋白质BAX，杀死不需要的或有缺陷的细胞，这一过程称为“细胞凋亡(apoptosis)”，。而哈佛大学的研究者认为他们找到了激活“细胞凋亡”过程的方法。
Loren Walensky博士说： “我们找到了能激活蛋白质BAX的物质，我们相信，可以籍此研发可以打开或关闭人体细胞死亡程序的药物，实现治疗目的。”
Walensky表示，其团队发现缩氨酸能恰到好处地激活“细胞凋亡”过程。当将缩氨酸放置到恰当位置时，蛋白质BAX会在为细胞提供能量的线粒体膜上击孔，从而杀死细胞。
Walensky认为，可借助这种机制来研发药物。 Walensky是位于麻省剑桥的生物技术公司Aileron Therapeutics的创始人之一。（生物谷Bioon.com）
生物谷推荐原始出处：
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.
