The heat shock-binding protein (HspBP1) protects cells against the cytotoxic action of the Tag7-Hsp70 complex.
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.
Institute of Gene Biology, Russian Academy of Sciences (RAS), Moscow 119344, Russia.
Denis V
DV
Yashin
Elena A
EA
Dukhanina
Olga D
OD
Kabanova
Elena A
EA
Romanova
Tamara I
TI
Lukyanova
Alexsander G
AG
Tonevitskii
Deborah A
DA
Raynes
Nikolai V
NV
Gnuchev
Vince
V
Guerriero
Georgii P
GP
Georgiev
Lidia P
LP
Sashchenko
D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D000255:Adenosine Triphosphate / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism*; D016207:Cytokines / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D003603:Cytotoxins / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D018840:HSP70 Heat-Shock Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D006801:Humans; D020014:K562 Cells; D051379:Mice; D046912:Multiprotein Complexes / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D009369:Neoplasms / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D011485:Protein Binding
D048868:Adaptor Proteins, Signal Transducing; D016207:Cytokines; D003603:Cytotoxins; D018840:HSP70 Heat-Shock Proteins; C116331:HSPBP1 protein, human; C483693:Hspa14 protein, human; D046912:Multiprotein Complexes; C491878:PGLYRP1 protein, human; D000255:Adenosine Triphosphate
Cell. 1998 Feb 6;92(3):351-66
9476895
Blood. 2005 Oct 1;106(7):2551-8
15956276
Cell Stress Chaperones. 2001 Oct;6(4):337-44
11795470
Cell. 2000 Apr 14;101(2):119-22
10786831
Annu Rev Immunol. 1986;4:651-80
3518752
Nat Cell Biol. 2001 Sep;3(9):839-43
11533664
J Biol Chem. 2007 Dec 7;282(49):35430-9
17855353
Genetika. 1996 May;32(5):621-8
8755036
Oncogene. 2003 Oct 2;22(43):6669-78
14555980
Biochem Mol Biol Int. 1994 May;33(1):73-80
7521704
J Biol Chem. 2003 May 23;278(21):19017-22
12651857
Dokl Biol Sci. 2007 May-Jun;414:246-8
17668634
Cell. 1990 Sep 7;62(5):875-87
1975516
Mol Immunol. 2004 Feb;40(12):877-86
14698226
J Mol Biol. 2005 Apr 8;347(4):683-91
15769462
J Immunoassay Immunochem. 2006;27(3):251-64
16827227
Proc Natl Acad Sci U S A. 1998 Aug 18;95(17):10078-82
9707603
Cell Mol Life Sci. 2005 Mar;62(6):670-84
15770419
J Biol Chem. 1998 Dec 4;273(49):32883-8
9830037
Cell. 2006 May 5;125(3):443-51
16678092
J Biol Chem. 2003 Oct 17;278(42):41173-81
12874291
Nature. 2001 Dec 13;414(6865):756-9
11742401
Mol Biol Cell. 2004 Sep;15(9):4003-10
15215316
Immunol Lett. 1994 Sep;42(1-2):97-100
7530233
FEBS Lett. 1998 Oct 30;438(1-2):1-4
9821948
Nat Cell Biol. 2000 Aug;2(8):469-75
10934466
J Biol Chem. 2004 Jan 16;279(3):2117-24
14585845
Proc Natl Acad Sci U S A. 2009 Aug 18;106(33):13963-7
19666596
EMBO J. 2001 Feb 1;20(3):446-56
11157751
Mol Cell. 2005 Feb 4;17(3):367-79
15694338
Nat Rev Mol Cell Biol. 2004 Oct;5(10):781-91
15459659
J Immunol. 1989 Sep 1;143(5):1453-60
2503557
Biol Cell. 2009 Jun;101(6):351-60
18986301
J Biol Chem. 1995 Feb 17;270(7):2967-73
7852376
Cancer Sci. 2009 Oct;100(10):1870-9
19659607
Blood. 2003 Jul 15;102(2):689-97
12649138
J Biol Chem. 1998 Jul 17;273(29):18633-9
9660837