近日,来自希伯来大学和魏茨曼科学研究所的研究人员发明出了一种可以促使细胞凋亡和程序性细胞死亡的方法,这或许为癌症治疗提供了新的见解,相关研究成果刊登在了国际著名杂志Journal of Biological Chemistry上。
细胞凋亡是机体必要的抵御异常细胞散布的防御机制,同时也是一个非常复杂的过程。癌症细胞通常由于某些基因的突变,可以逃避细胞凋亡的过程进而使癌症扩散。在研究中,研究者Gross检测了涉及细胞凋亡的两个重要蛋白质之间的相互作用,其中一种蛋白质是线粒体载体同源物2(MTCH2),是在研究者Gross实验室发现的;另外一种是截短体BID(tBID),这两种蛋白质都参与了细胞凋亡的过程。研究者发现两种蛋白质的某种序列可以互相进行结合,这是细胞凋亡起始的重要步骤。紧接着研究者的发现,他们发明出了短的蛋白合成序列,或者肽类,并且合成出的肽类可以模仿上述两种蛋白质的区域进行相互结合,而且研究者也可以抑制这种结合作用。
研究者Friedler表示,这种蛋白质片段或许成为将来抗癌疗法的基础,我们已经揭开了蛋白质相互作用潜在的面纱,这将成为开发抗癌药物的潜在靶点,这种新型的抗癌药物可以通过干扰蛋白的相互作用来激活细胞凋亡。(生物谷Bioon.com)
编译自:New Way to Induce Programmed Cell Death, or Apoptosis
doi:10.1074/jbc.M111.328377
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PMID:
Molecular Basis of the Interaction between Proapoptotic Truncated BID (tBID) Protein and Mitochondrial Carrier Homologue 2 (MTCH2) Protein KEY PLAYERS IN MITOCHONDRIAL DEATH PATHWAY
Chen Katz‡, Yehudit Zaltsman-Amir§, Yana Mostizky§, Neta Kollet‡, Atan Gross§,1 and Assaf Friedler‡,2
The molecular basis of the interaction between mitochondrial carrier homologue 2 (MTCH2) and truncated BID (tBID) was characterized. These proteins participate in the apoptotic pathway, and the interaction between them may serve as a target for anticancer lead compounds. In response to apoptotic signals, MTCH2 recruits tBID to the mitochondria, where it activates apoptosis. A combination of peptide arrays screening with biochemical and biophysical techniques was used to characterize the mechanism of the interaction between tBID and MTCH2 at the structural and molecular levels. The regions that mediate the interaction between the proteins were identified. The two specific binding sites between the proteins were determined to be tBID residues 59–73 that bind MTCH2 residues 140–161, and tBID residues 111–125 that bind MTCH2 residues 240–290. Peptides derived from tBID residues 111–125 and 59–73 induced cell death in osteosarcoma cells. These peptides may serve as lead compounds for anticancer drugs that act by targeting the tBID-MTCH2 interaction.