Tag7 (PGLYRP1) in Complex with Hsp70 Induces Alternative Cytotoxic Processes in Tumor Cells via TNFR1 Receptor.

Tag7 (also known as peptidoglycan recognition protein PGRP-S, PGLYRP1), an innate immunity protein, interacts with Hsp70 to form a stable Tag7-Hsp70 complex with cytotoxic activity against some tumor cell lines. In this study, we have analyzed the programmed cell death mechanisms that are induced when cells interact with the Tag7-Hsp70 complex, which was previously shown to be released by human lymphocytes and is cytotoxic to cancer cells. We show that this complex induces both apoptotic and necroptotic processes in the cells. Apoptosis follows the classic caspase-8 and caspase-3 activation pathway. Inhibition of apoptosis leads to a switch to the RIP1-dependent necroptosis. Both of these cytotoxic processes are initiated by the involvement of TNFR1, a receptor for TNF-α. Our results suggest that the Tag7-Hsp70 complex is a novel ligand for this receptor. One of its components, the innate immunity protein Tag7, can bind to the TNFR1 receptor, thereby inhibiting the cytotoxic actions of the Tag7-Hsp70 complex and TNF-α, an acquired immunity cytokine.
AuthorsDenis V Yashin, Olga K Ivanova, Natalia V Soshnikova, Anton A Sheludchenkov, Elena A Romanova, Elena A Dukhanina, Alexander G Tonevitsky, Nikolai V Gnuchev, Alexander G Gabibov, Georgii P Georgiev, Lidia P Sashchenko
JournalThe Journal of biological chemistry (J Biol Chem) Vol. 290 Issue 35 Pg. 21724-31 (Aug 28 2015) ISSN: 1083-351X [Electronic] United States
PMID26183779 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Copyright© 2015 by The American Society for Biochemistry and Molecular Biology, Inc.
Chemical References
  • Cytokines
  • HSP70 Heat-Shock Proteins
  • PGLYRP1 protein, human
  • Receptors, Tumor Necrosis Factor, Type I
  • Tumor Necrosis Factor-alpha
  • Caspases
  • Animals
  • Apoptosis
  • Caspases (metabolism)
  • Cell Line
  • Clone Cells
  • Cytokines (metabolism)
  • HEK293 Cells
  • HSP70 Heat-Shock Proteins (metabolism)
  • Humans
  • Mice
  • Necrosis
  • Protein Binding
  • Receptors, Tumor Necrosis Factor, Type I (metabolism)
  • Tumor Necrosis Factor-alpha (metabolism)

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