Peptidoglycan recognition protein tag7 forms a cytotoxic complex with heat shock protein 70 in solution and in lymphocytes.
The peptidoglycan recognition protein Tag7 is shown to form a stable 1:1 complex with the major stress protein Hsp70. Neither protein is cytotoxic by itself, but their complex induces apoptotic death in several tumor-derived cell lines even at subnanomolar concentrations. The minimal part of Hsp70 needed to evoke cytotoxicity is residues 450-463 of its peptide-binding domain, but full cytotoxicity requires its ATPase activity; remarkably, Tag7 liberated from the complex at high ATP is not cytotoxic. The Tag7-Hsp70 complex is produced by tag7-transfected cells and by lymphokine-activated killers, being assembled within the cell and released into the medium through the Golgi apparatus by a mechanism different from the commonly known granule exocytosis. Thus, we demonstrate how a heat shock protein may perform functions clearly distinct from chaperoning or cell rescue and how peptidoglycan recognition proteins may be involved in innate immunity and anti-cancer defense.
Institute of Gene Biology, Russian Academy of Sciences, Moscow 117334, Russia.
Lidia P
LP
Sashchenko
Elena A
EA
Dukhanina
Denis V
DV
Yashin
Yurii V
YV
Shatalov
Elena A
EA
Romanova
Elena V
EV
Korobko
Alexander V
AV
Demin
Tamara I
TI
Lukyanova
Olga D
OD
Kabanova
Sergei V
SV
Khaidukov
Sergei L
SL
Kiselev
Alexander G
AG
Gabibov
Nikolai V
NV
Gnuchev
Georgii P
GP
Georgiev
D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D017209:Apoptosis; D002352:Carrier Proteins / Q000737:chemistry* / Q000502:physiology; D002478:Cells, Cultured; D016207:Cytokines / Q000737:chemistry* / Q000502:physiology; D003602:Cytotoxicity, Immunologic; D018840:HSP70 Heat-Shock Proteins / Q000737:chemistry* / Q000502:physiology; D006801:Humans; D006868:Hydrolysis; D008214:Lymphocytes / Q000276:immunology* / Q000378:metabolism; D051379:Mice; D012996:Solutions
D002352:Carrier Proteins; D016207:Cytokines; D018840:HSP70 Heat-Shock Proteins; C491878:PGLYRP1 protein, human; C113582:Pglyrp1 protein, mouse; D012996:Solutions; C118897:peptidoglycan recognition protein; D000255:Adenosine Triphosphate