The Heat Shock-binding Protein (HspBP1) Protects Cells against the Cytotoxic Action of the Tag7-Hsp70 Complex

Abstract

Heat shock-binding protein HspBP1 is a member of the Hsp70 co-chaperone family. The interaction between HspBP1 and the ATPase domain of the major heat shock protein Hsp70 up-regulates nucleotide exchange and reduces the affinity between Hsp70 and the peptide in its peptide-binding site. Previously we have shown that Tag7 (also known as peptidoglycan recognition protein PGRP-S), an innate immunity protein, interacts with Hsp70 to form a stable Tag7-Hsp70 complex with cytotoxic activity against some tumor cell lines. This complex can be produced in cytotoxic lymphocytes and released during interaction with tumor cells. Here the effect of HspBP1 on the cytotoxic activity of the Tag7-Hsp70 complex was examined. HspBP1 could bind not only to Hsp70, but also to Tag7. This interaction eliminated the cytotoxic activity of Tag7-Hsp70 complex and decreased the ATP concentration required to dissociate Tag7 from the peptide-binding site of Hsp70. Moreover, HspBP1 inhibited the cytotoxic activity of the Tag7-Hsp70 complex secreted by lymphocytes. HspBP1 was detected in cytotoxic CD8؉ lymphocytes. This protein was released simultaneously with Tag7-Hsp70 during interaction of these lymphocytes with tumor cells. The simultaneous secretion of the cytotoxic complex with its inhibitor could be a mechanism protecting normal cells from the cytotoxic effect of this complex.

Peptidoglycan recognition protein–peptidoglycan complexes increase monocyte/macrophage activation and enhance the inflammatory response

“…It was previously reported that PGRP‐S forms a potent cytotoxic complex with heat‐shock protein 70, which induces apoptotic death in various tumour lines . We observed that PGRP are able to protect membrane damage produced by PGN in normal cells.…”

A new role for PGRP-S (Tag7) in immune defense: lymphocyte migration is induced by a chemoattractant complex of Tag7 with Mts1

“…9, 17 Moreover, we have found 2 additional proteins that can interact with Tag7: the Ca 2C -binding protein S100A4 (Mts1), encoded by the gene that is highly expressed in metastatic tumors and cells of the immune system, and the cochaperone HspBP1, which inhibits the ATPase activity of Hsp70. [18][19][20][21] Their interaction with Tag7 results in the suppression of cytotoxicity of the Tag-Hsp70 complex.…”

The Vasculome of the Mouse Brain

“…PGLYRPs (or PGRPs, peptidoglycan recognition proteins) have four isoforms, PGLYRP1-4, that function in antibacterial immunity and inflammation [50]. PGLYRP1 can bind with the key stress response proteins such as Hsp70 and S100A4 to trigger cytotxicity for antibacterial activity [51], [52]. Expression pglyrp1 in the brain have been reported, but its endothelial function is currently unknown [53].…”