Antigen: human Hsp70 · Clone designation: C92F3A-5 · Host: rabbit · Application(s): WB, IP, ICC, EIA, and IHC · Hsp70 genes encode abundant heat-inducible 70 kDa Hsps (Hsp70). In most eukaryotes Hsp70 genes exist as part of a multigene family. They are found in most cellular compartments of eukaryotes including nuclei, mitochondria, chloroplasts, the endoplasmic reticulum, and the cytosol, as well as in bacteria. The genes show a high degree of conservation, having at least 50% identity.¹ The N-terminal two thirds of Hsp70s are more conserved than the C-terminal third. Hsp70 binds ATP with high affinity and possesses a weak ATPase activity which can be stimulated by binding to unfolded proteins and synthetic peptides.² When Hsc70 (constitutively expressed) present in mammalian cells was truncated, ATP binding activity was found to reside in an N-terminal fragment of 44 kDa which lacked peptide binding capacity. Polypeptide binding ability therefore resided within the C-terminal half.³ The structure of this ATP binding domain displays multiple features of nucleotide binding proteins.⁴ All Hsp70s, regardless of location, bind proteins, particularly unfolded ones. The molecular chaperones of the Hsp70 family recognize and bind to nascent polypeptide chains as well as partially folded intermediates of proteins preventing their aggregation and misfolding. The binding of ATP triggers a bound substrate protein.⁵ The universal ability of Hsp70s to undergo cycles of binding to and release from hydrophobic stretches of partially unfolded proteins determines their role in a great variety of vital intracellular functions such as protein synthesis, protein folding, oligomerization, and protein transport.

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4 Bork, P., Sander, C., and Valencia, A. An ATPase domain common to prokaryotic cell cycle proteins, sugar kinases, actin, and hsp70 heat shock proteins. Proc Natl Acad Sci USA 89 7290-7294 (1992).

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Moon, I.S., Park, I.S., Schenker, L.T., et al. Presence of both constitutive and inducible forms of heat shock protein 70 in the cerebral cortex and hippocampal synapses. Cereb Cortex 11 238-248 (2001).

Boorstein, W.R., Ziegelhoffer, T., and Craig, E.A. Molecular evolution of the HSP70 multigene family. J Mol Evol 38(1) 1-17 (1994).

Fink, A.L. Chaperone-mediated protein folding. Physiol Rev 79(2) 425-449 (1999).

Bork, P., Sander, C., and Valencia, A. An ATPase domain common to prokaryotic cell cycle proteins, sugar kinases, actin, and hsp70 heat shock proteins. Proc Natl Acad Sci USA 89 7290-7294 (1992).

DeLuca-Flaherty, C., McKay, D.B., Parham, P., et al. Uncoating protein (hsc70) binds a conformationally labile domain of clathrin light chain LCa to stimulate ATP hydrolysis. Cell 62 875-887 (1990).

Rothman, J.E. Polypeptide chain binding proteins: Catalysts of protein folding and related processes in cells. Cell 59 591-601 (1989).

Dressel, R., Elsner, L., Quentin, T., et al. Heat shock protein 70 is able to prevent heat shock-induced resistance of target cells to CTL. J Immunol 164 2362-2371 (2000).

Pockley, A.G., Shepherd, J., and Corton, J.M. Detection of heat shock protein 70 (HSP70) and anti-HSP70 antibodies in the serum of normal individuals. Immunol Invest 27(6) 367-377 (1998).

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Kondo, T., Matsuda, T., Tashima, M., et al. Suppression of heat shock protein-70 by ceramide in heat shock-induced HL-60 cell apoptosis. J Biol Chem 275(12) 8872-8879 (2000).

Misaki, T., Takeuchi, R., Miyamoto, S., et al. Induction in vitro of 72-kD heat shock protein in a continuous culture or rat thyroid cells, FRTL5. Clin Exp Immunol 98 234-239 (1994).

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