近日，來自希伯來大學和魏茨曼科學研究所的研究人員發(fā)明出了一種可以促使細胞凋亡和程序性細胞死亡的方法,，這或許為癌癥治療提供了新的見解,，相關研究成果刊登在了國際著名雜志Journal of Biological Chemistry上,。
細胞凋亡是機體必要的抵御異常細胞散布的防御機制，同時也是一個非常復雜的過程,。癌癥細胞通常由于某些基因的突變,，可以逃避細胞凋亡的過程進而使癌癥擴散。在研究中,，研究者Gross檢測了涉及細胞凋亡的兩個重要蛋白質之間的相互作用,，其中一種蛋白質是線粒體載體同源物2（MTCH2），是在研究者Gross實驗室發(fā)現的,；另外一種是截短體BID（tBID）,，這兩種蛋白質都參與了細胞凋亡的過程。研究者發(fā)現兩種蛋白質的某種序列可以互相進行結合,，這是細胞凋亡起始的重要步驟,。緊接著研究者的發(fā)現,，他們發(fā)明出了短的蛋白合成序列，或者肽類,，并且合成出的肽類可以模仿上述兩種蛋白質的區(qū)域進行相互結合,，而且研究者也可以抑制這種結合作用。
研究者Friedler表示,，這種蛋白質片段或許成為將來抗癌療法的基礎,，我們已經揭開了蛋白質相互作用潛在的面紗,，這將成為開發(fā)抗癌藥物的潛在靶點,，這種新型的抗癌藥物可以通過干擾蛋白的相互作用來激活細胞凋亡。（生物谷Bioon.com）
編譯自：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.
