Regulation of Signaling Protein Function and Trafficking by the hsp90/hsp70-Based Chaperone Machinery
Tóm tắt
Nearly 100 proteins are known to be regulated by hsp90. Most of these substrates or “client proteins” are involved in signal transduction, and they are brought into complex with hsp90 by a multlprotein hsp90/hsp70-based chaperone machinery. In addition to binding substrate proteins at the chaperone site(s), hsp90 binds cofactors at other sites that are part of the heterocomplex assembly machinery as well as immunophllins that connect assembled substrate·hsp90 complexes to protein-trafficking systems. In the 5 years since we last reviewed this subject, much has been learned about hsp90 structure, nucleotide-binding, and cochaperone interactions; the most important concept is that ATP hydrolysis by an intrinsic ATPase activity results in a conformational change in hsp90 that is required to induce conformational change in a substrate protein. The conformational change induced in steroid receptors is an opening of the steroid-binding cleft so that it can be accessed by steroid. We have now developed a minimal system of five purified proteins—hsp90, hsp70, Hop, hsp40, and p23—that assembles stable receptor·hsp90 heterocomplexes. An hsp90·Hop·hsp70·hsp40 complex opens the cleft in an ATP-dependent process to produce a receptor·hsp90 heterocomplex with hsp90 in its ATP-bound conformation, and p23 then interacts with the hsp90 to stabilize the complex. Stepwise assembly experiments have shown that hsp70 and hsp40 first interact with the receptor in an ATP-dependent reaction to produce a receptor·hsp70·hsp40 complex that is “primed” to be activated to the steroid-binding state in a second ATP-dependent step with hsp90, Hop, and p23. Successful use of the five-protein system with other substrates Indicates that it can assemble signal protein-hsp90 heterocomplexes whether the substrate is a receptor, a protein kinase, or a transcription factor. This purified system should facilitate understanding of how eukaryotlc hsp70 and hsp90 work together as essential components of a process that alters the conformations of substrate proteins to states that respond in signal transduction.
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Tài liệu tham khảo
Pratt WB, 1997, Endocr Rev, 18, 18
Beissinger M, 1998, Biol Chem, 379, 379
Csermely P, 1998, A comprehensive review. Pharmacol Ther, 79, 79
Krishna P, 2001, Arabidopsis thaliana. Cell Stress Chaperones, 6, 6, 10.1379/1466-1268(2001)006<0006:AIRAPA>2.0.CO;2
Smith DF, 2000, Cell Devel Biol, 11, 11
Xu M, 1998, J Biol Chem, 273, 273
Whitesell L, 1996, Mol Endo, 10, 10
Schuh S, 1985, pp60v-src J Biol Chem, 260, 260
Redeuilh G, 1987, J Biol Chem, 262, 262
Rafestin-Oblin ME, 1989, Oligomeric structure and transformation. J Biol Chem, 264, 264
Perdew GH, 1988, J Biol Chem, 263, 263
Zuo J, 1998, Cell, 94, 94
Hutchison KA, 1992, J Biol Chem, 267, 267
An WG, 2000, Cell Growth Differentiation, 11, 11
Scholz GM, 2001, Cell Growth Diff, 12, 12
Yang J, 2001, Cancer Res, 61, 61
Lovrich J, 1994, FEBS Lett, 343, 343
Louvion J-F, 1988, Mol Biol Cell, 9, 9
Stancato LF, 1997, J Biol Chem, 271, 271
Flanagan CH, 1992, J Biol Chem, 267, 267
de Career G, 2001, EMBO J, 20, 20
Abbas-Terki T, 1999, An in vivo model substrate for the molecular chaperone heat-shock protein 90 in yeast. Eur J Biochem, 266, 266
Johnson JL, 1994, J Biol Chem, 269, 269
Chang H-CJ, 1994, J Biol Chem, 269, 269
Creve G, 2001, J Cell Sci, 114, 114
Smith DF, 1993, J Biol Chem, 268, 268
Chen S, 1996, Mol Endocrinol, 10, 10
Lassie M, 1997, J Biol Chem, 272, 272
Jiang J, 2001, Identification of hsc70 as a target for ubiquitylation. J Biol Chem, 276, 276
Brugge JS, 1996, Curr Topics Microbial Immunol, 123, 123
Dutta R, 2000, TIBS, 25, 25
Freeman BC, 2000, Genes &Development, 14, 14
Argon Y, 1999, Cell &Development Biol, 10, 10
Barrai JM, 2002, Science, 295, 295
Hutchison KA, 1992, J Biol Chem, 267, 267
Hutchison KA, 1994, J Biol Chem, 269, 269
Smith DF, 1993, Mol Endocrinol, 7, 7
Hutchison KA, 1994, a “foldosome.” J Biol Chem, 269, 269
Prapapanich V, 1996, Mol Endocrinol, 10, 10
Höhfeld J, 1995, Cell, 83, 83
Fiss AE, 1999, J Biol Chem, 274, 274
Johnson JL, 1995, Mol Endocrinol, 9, 9
Kanalakis KC, 2002, J Biol Chem, 277, 277
O'Brien MC, 1995, I. Potassium is required for optimal ATPase activity. J Biol Chem, 270, 270
Wilbanks SM, 1995, II. Potassium binds specifically in the ATPase active site. J Biol Chem, 270, 270
DeFranco DB, 1995, Vitam Horm, 51, 51
Czar MJ, 1994, Mol Endocrinol, 8, 8
Czar MJ, 1995, Mol Endocrinol, 9, 9
Davies TH, 2002, Hormone-induced switching of FKBP51 and FKBP52 immunophilins. J Biol Chem, 277, 277