Granulysin Induces Cathepsin B Release from Lysosomes of Target Tumor Cells to Attack Mitochondria through Processing of Bid Leading to Necroptosis

作者: Honglian Zhang , Chao Zhong , Lei Shi , Yuming Guo , Zusen Fan

DOI: 10.4049/JIMMUNOL.0802502

关键词:

摘要: Granulysin is a killer effector molecule localized in cytolytic granules of human NK and CTL cells. exhibits broad antimicrobial activity potent cytotoxic action against tumor However, the molecular mechanism granulysin-induced lysis poorly understood. In this study, we found that granulysin causes novel cell death termed necroptosis. can target lysosomes cells induce partial release lysosomal contents into cytosol. Relocalized cathepsin B process Bid to active tBid cause cytochrome c apoptosis-activating factor from mitochondria. Cathepsin silencing or Bax/Bak deficiency resists less susceptible cytolysis

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