The Tag7-Hsp70 cytotoxic complex induces tumor cell necroptosis via permeabilisation of lysosomes and mitochondria.

摘要: Tag7 (PGRP-S, or PGLYRP1), an innate immunity protein, plays important role in the immune defense system. It forms a stable cytotoxic complex with heat shock protein Hsp70. This can induce apoptotic necroptotic tumor cell death by interacting TNFR1 receptor. In this study, we analyzed molecular events involved process of Tag7-Hsp70-induced necroptosis. We found that bind to sTNFR1, soluble fragment receptor, leading inhibition RIP1 dependent A major downstream phases Tag7-Hsp70 induced necroptosis was played interaction between lysosomes and mitochondria. The receptor triggered certain sequence events: at first, it activated kinase, later on, increased intracellular concentration Са(2+) ions activation calpains, which led permeabilization lysosomal membranes. consequent release enzymes, including cathepsins B D, resulted depolarization mitochondrial membrane, ROS production, eventual death.