The heat shock proteins: Their roles as multi-component machines for protein folding

Fungal Biology Reviews

Volumn 22, Issue 3-4, 2008, Pages 110-119

  Panaretou, Barry ^a   Zhai, Chao ^a  

^a KING'S COLLEGE LONDON   (United Kingdom)

Author keywords

Chaperones; Heat shock proteins

Indexed keywords

FUNGI;

EID: 67349101754     PISSN: 17494613     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.fbr.2009.04.002     Document Type: Review

References (105)

1. Ali M.M., Roe S.M., Vaughan C.K., Meyer P., Panaretou B., Piper P.W., Prodromou C., and Pearl L.H. Crystal structure of an Hsp90-nucleotide-p23/Sba1 closed chaperone complex. Nature 440 (2006) 1013-1017
2. Aligue R., Akhavan-Niak H., and Russell P. A role for Hsp90 in cell cycle control: Wee1 tyrosine kinase activity requires interaction with Hsp90. EMBO J. 13 (1994) 6099-6106
3. Bali M., Zhang B., Morano K.A., and Michels C.A. The Hsp90 molecular chaperone complex regulates maltose induction and stability of the Saccharomyces MAL gene transcription activator Mal63p. J. Biol. Chem. 278 (2003) 47441-47448
4. Bentley N.J., Fitch I.T., and Tuite M.F. The small heat-shock protein Hsp26 of Saccharomyces cerevisiae assembles into a high molecular weight aggregate. Yeast 8 (1992) 95-106
5. Borkovich K.A., Farrelly F.W., Finkelstein D.B., Taulien J., and Lindquist S. hsp82 is an essential protein that is required in higher concentrations for growth of cells at higher temperatures. Mol. Cell. Biol. 9 (1989) 3919-3930
6. Bosl B., Grimminger V., and Walter S. Substrate binding to the molecular chaperone Hsp104 and its regulation by nucleotides. J. Biol. Chem. 280 (2005) 38170-38176
7. Bossier P., Fitch I.T., Boucherie H., and Tuite M.F. Structure and expression of a yeast gene encoding the small heat-shock protein Hsp26. Gene 78 (1989) 323-330
8. Braley R., and Piper P.W. The C-terminus of yeast plasma membrane H+-ATPase is essential for the regulation of this enzyme by heat shock protein Hsp30, but not for stress activation. FEBS Lett. 418 (1997) 123-126
9. Cashikar A.G., Duennwald M., and Lindquist S.L. A chaperone pathway in protein disaggregation. Hsp26 alters the nature of protein aggregates to facilitate reactivation by Hsp104. J. Biol. Chem. 280 (2005) 23869-23875
10. Catlett M.G., and Kaplan K.B. Sgt1p is a unique co-chaperone that acts as a client adaptor to link Hsp90 to Skp1p. J. Biol. Chem. 281 (2006) 33739-33748
11. Cheng M.Y., Hartl F.U., Martin J., Pollock R.A., Kalousek F., Neupert W., Hallberg E.M., Hallberg R.L., and Horwich A.L. Mitochondrial heat-shock protein hsp60 is essential for assembly of proteins imported into yeast mitochondria. Nature 337 (1989) 620-625
12. Chernoff Y.O., Lindquist S.L., Ono B., Inge-Vechtomov S.G., and Liebman S.W. Role of the chaperone protein Hsp104 in propagation of the yeast prion-like factor [PSI+]. Science 268 (1995) 880-884
13. Cowen L.E., and Lindquist S. Hsp90 potentiates the rapid evolution of new traits: drug resistance in diverse fungi. Science 309 (2005) 2185-2189
14. Cowen L.E., Carpenter A.E., Matangkasombut O., Fink G.R., and Lindquist S. Genetic architecture of Hsp90-dependent drug resistance. Eukaryot. Cell 5 (2006) 2184-2188
15. Davidson J.F., and Schiestl R.H. Cytotoxic and genotoxic consequences of heat stress are dependent on the presence of oxygen in Saccharomyces cerevisiae. J. Bacteriol. 183 (2001) 4580-4587
16. Deloche O., Kelley W.L., and Georgopoulos C. Structure-function analyses of the Ssc1p, Mdj1p, and Mge1p Saccharomyces cerevisiae mitochondrial proteins in Escherichia coli. J. Bacteriol. 179 (1997) 6066-6075
17. Demoinet E., Jacquier A., Lutfalla G., and Fromont-Racine M. The Hsp40 chaperone Jjj1 is required for the nucleo-cytoplasmic recycling of preribosomal factors in Saccharomyces cerevisiae. RNA 13 (2007) 1570-1581
18. Donze O., and Picard D. Hsp90 binds and regulates Gcn2, the ligand-inducible kinase of the alpha subunit of eukaryotic translation initiation factor 2 [corrected]. Mol. Cell. Biol. 19 (1999) 8422-8432
19. Dragovic Z., Broadley S.A., Shomura Y., Bracher A., and Hartl F.U. Molecular chaperones of the Hsp110 family act as nucleotide exchange factors of Hsp70s. EMBO J. 25 (2006) 2519-2528
20. Duina A.A., Marsh J.A., Kurtz R.B., Chang H.C., Lindquist S., and Gaber R.F. The peptidyl-prolyl isomerase domain of the CyP-40 cyclophilin homolog Cpr7 is not required to support growth or glucocorticoid receptor activity in Saccharomyces cerevisiae. J. Biol. Chem. 273 (1998) 10819-10822
21. Eaglestone S.S., Cox B.S., and Tuite M.F. Translation termination efficiency can be regulated in Saccharomyces cerevisiae by environmental stress through a prion-mediated mechanism. EMBO J. 18 (1999) 1974-1981
22. Fan C.Y., Lee S., and Cyr D.M. Mechanisms for regulation of Hsp70 function by Hsp40. Cell Stress Chaperones 8 (2003) 309-316
23. Floer M., Bryant G.O., and Ptashne M. HSP90/70 chaperones are required for rapid nucleosome removal upon induction of the GAL genes of yeast. Proc. Natl. Acad. Sci. U.S.A. 105 (2008) 2975-2980
24. Franzmann T.M., Wuhr M., Richter K., Walter S., and Buchner J. The activation mechanism of Hsp26 does not require dissociation of the oligomer. J. Mol. Biol. 350 (2005) 1083-1093
25. Franzmann T.M., Menhorn P., Walter S., and Buchner J. Activation of the chaperone Hsp26 is controlled by the rearrangement of its thermosensor domain. Mol. Cell 29 (2008) 207-216
26. Galeote V.A., Alexandre H., Bach B., Delobel P., Dequin S., and Blondin B. Sfl1p acts as an activator of the HSP30 gene in Saccharomyces cerevisiae. Curr. Genet. 52 (2007) 55-63
27. Glover J.R., and Lindquist S. Hsp104, Hsp70, and Hsp40: a novel chaperone system that rescues previously aggregated proteins. Cell 94 (1998) 73-82
28. Hainzl O., Wegele H., Richter K., and Buchner J. Cns1 is an activator of the Ssa1 ATPase activity. J. Biol. Chem. 279 (2004) 23267-23273
29. Haslbeck M., Walke S., Stromer T., Ehrnsperger M., White H.E., Chen S., Saibil H.R., and Buchner J. Hsp26: a temperature-regulated chaperone. EMBO J. 18 (1999) 6744-6751
30. Haslbeck M., Braun N., Stromer T., Richter B., Model N., Weinkauf S., and Buchner J. Hsp42 is the general small heat shock protein in the cytosol of Saccharomyces cerevisiae. EMBO J. 23 (2004) 638-649
31. Haslbeck M., Miess A., Stromer T., Walter S., and Buchner J. Disassembling protein aggregates in the yeast cytosol. The cooperation of Hsp26 with Ssa1 and Hsp104. J. Biol. Chem. 280 (2005) 23861-23868
32. Horwitz J. Alpha-crystallin can function as a molecular chaperone. Proc. Natl. Acad. Sci. U.S.A. 89 (1992) 10449-10453
33. Jakob U., Gaestel M., Engel K., and Buchner J. Small heat shock proteins are molecular chaperones. J. Biol. Chem. 268 (1993) 1517-1520
34. Jang Y.J., Park S.K., and Yoo H.S. Isolation of an HSP12-homologous gene of Schizosaccharomyces pombe suppressing a temperature-sensitive mutant allele of cdc4. Gene 172 (1996) 125-129
35. Johnson J.L., and Toft D.O. A novel chaperone complex for steroid receptors involving heat shock proteins, immunophilins, and p23. J. Biol. Chem. 269 (1994) 24989-24993
36. Jones G.W., and Tuite M.F. Chaperoning prions: the cellular machinery for propagating an infectious protein?. BioEssays 27 (2005) 823-832
37. Jung G., Jones G., Wegrzyn R.D., and Masison D.C. A role for cytosolic hsp70 in yeast [PSI+] prion propagation and [PSI+] as a cellular stress. Genetics 156 (2000) 559-570
38. Kabani M., Beckerich J.M., and Gaillardin C. Sls1p stimulates Sec63p-mediated activation of Kar2p in a conformation-dependent manner in the yeast endoplasmic reticulum. Mol. Cell. Biol. 20 (2000) 6923-6934
39. Kabani M., Beckerich J.M., and Brodsky J.L. Nucleotide exchange factor for the yeast Hsp70 molecular chaperone Ssa1p. Mol. Cell. Biol. 22 (2002) 4677-4689
40. Karreman R.J., Dague E., Gaboriaud F., Quiles F., Duval J.F., and Lindsey G.G. The stress response protein Hsp12p increases the flexibility of the yeast Saccharomyces cerevisiae cell wall. Biochim. Biophys. Acta 1774 (2007) 131-137
41. Kaufman B.A., Kolesar J.E., Perlman P.S., and Butow R.A. A function for the mitochondrial chaperonin Hsp60 in the structure and transmission of mitochondrial DNA nucleoids in Saccharomyces cerevisiae. J. Cell. Biol. 163 (2003) 457-461
42. Kim S., Schilke B., Craig E.A., and Horwich A.L. Folding in vivo of a newly translated yeast cytosolic enzyme is mediated by the SSA class of cytosolic yeast Hsp70 proteins. Proc. Natl. Acad. Sci. U.S.A. 95 (1998) 12860-12865
43. Kryndushkin D., and Wickner R.B. Nucleotide exchange factors for Hsp70s are required for [URE3] prion propagation in Saccharomyces cerevisiae. Mol. Biol. Cell 18 (2007) 2149-2154
44. Kubo Y., Tsunehiro T., Nishikawa S., Nakai M., Ikeda E., Toh-e A., Morishima N., Shibata T., and Endo T. Two distinct mechanisms operate in the reactivation of heat-denatured proteins by the mitochondrial Hsp70/Mdj1p/Yge1p chaperone system. J. Mol. Biol. 286 (1999) 447-464
45. Kucej M., Kucejova B., Subramanian R., Chen X.J., and Butow R.A. Mitochondrial nucleoids undergo remodeling in response to metabolic cues. J. Cell Sci. 121 (2008) 1861-1868
46. Kushnirov V.V., Kryndushkin D.S., Boguta M., Smirnov V.N., and Ter-Avanesyan M.D. Chaperones that cure yeast artificial [PSI+] and their prion-specific effects. Curr. Biol. 10 (2000) 1443-1446
47. Lan C., Lee H.C., Tang S., and Zhang L. A novel mode of chaperone action: heme activation of Hap1 by enhanced association of Hsp90 with the repressed Hsp70-Hap1 complex. J. Biol. Chem. 279 (2004) 27607-27612
48. Louvion J.F., Abbas-Terki T., and Picard D. Hsp90 is required for pheromone signaling in yeast. Mol. Biol. Cell 9 (1998) 3071-3083
49. Lutz T., Westermann B., Neupert W., and Herrmann J.M. The mitochondrial proteins Ssq1 and Jac1 are required for the assembly of iron sulfur clusters in mitochondria. J. Mol. Biol. 307 (2001) 815-825
50. Lyman S.K., and Schekman R. Interaction between BiP and Sec63p is required for the completion of protein translocation into the ER of Saccharomyces cerevisiae. J. Cell. Biol. 131 (1995) 1163-1171
51. MacLean M., and Picard D. Cdc37 goes beyond Hsp90 and kinases. Cell Stress Chaperones 8 (2003) 114-119
52. Marsh J.A., Kalton H.M., and Gaber R.F. Cns1 is an essential protein associated with the hsp90 chaperone complex in Saccharomyces cerevisiae that can restore cyclophilin 40-dependent functions in cpr7Δ cells. Mol. Cell. Biol. 18 (1998) 7353-7359
53. Mayer M.P., and Bukau B. Hsp70 chaperones: cellular functions and molecular mechanism. Cell. Mol. Life Sci. 62 (2005) 670-684
54. Meyer A.E., Hung N.J., Yang P., Johnson A.W., and Craig E.A. The specialized cytosolic J-protein, Jjj1, functions in 60S ribosomal subunit biogenesis. Proc. Natl. Acad. Sci. U.S.A. 104 (2007) 1558-1563
55. Millson S.H., Truman A.W., King V., Prodromou C., Pearl L.H., and Piper P.W. A two-hybrid screen of the yeast proteome for Hsp90 interactors uncovers a novel Hsp90 chaperone requirement in the activity of a stress-activated mitogen-activated protein kinase, Slt2p (Mpk1p). Eukaryot. Cell 4 (2005) 849-860
56. Mosser D.D., Ho S., and Glover J.R. Saccharomyces cerevisiae Hsp104 enhances the chaperone capacity of human cells and inhibits heat stress-induced proapoptotic signaling. Biochemistry 43 (2004) 8107-8115
57. Mukai H., Kuno T., Tanaka H., Hirata D., Miyakawa T., and Tanaka C. Isolation and characterization of SSE1 and SSE2, new members of the yeast HSP70 multigene family. Gene 132 (1993) 57-66
58. Nathan D.F., and Lindquist S. Mutational analysis of Hsp90 function: interactions with a steroid receptor and a protein kinase. Mol. Cell. Biol. 15 (1995) 3917-3925
59. Okamura K., Kimata Y., Higashio H., Tsuru A., and Kohno K. Dissociation of Kar2p/BiP from an ER sensory molecule, Ire1p, triggers the unfolded protein response in yeast. Biochem. Biophys. Res. Commun. 279 (2000) 445-450
60. Panaretou B., and Piper P.W. The plasma membrane of yeast acquires a novel heat-shock protein (Hsp30) and displays a decline in proton-pumping ATPase levels in response to both heat shock and the entry to stationary phase. Eur. J. Biochem. 206 (1992) 635-640
61. Panaretou B., Prodromou C., Roe S.M., O'Brien R., Ladbury J.E., Piper P.W., and Pearl L.H. ATP binding and hydrolysis are essential to the function of the Hsp90 molecular chaperone in vivo. EMBO J. 17 (1998) 4829-4836
62. Panaretou B., Siligardi G., Meyer P., Maloney A., Sullivan J.K., Singh S., Millson S.H., Clarke P.A., Naaby-Hansen S., Stein R., Cramer R., Mollapour M., Workman P., Piper P.W., Pearl L.H., and Prodromou C. Activation of the ATPase activity of hsp90 by the stress-regulated cochaperone aha1. Mol. Cell 10 (2002) 1307-1318
63. Parsell D.A., Sanchez Y., Stitzel J.D., and Lindquist S. Hsp104 is a highly conserved protein with two essential nucleotide-binding sites. Nature 353 (1991) 270-273
64. Parsell D.A., Kowal A.S., and Lindquist S. Saccharomyces cerevisiae Hsp104 protein. Purification and characterization of ATP-induced structural changes. J. Biol. Chem. 269 (1994) 4480-4487
65. Pearce D.A., Ferea T., Nosel S.A., Das B., and Sherman F. Action of BTN1, the yeast orthologue of the gene mutated in Batten disease. Nat. Genet. 22 (1999) 55-58
66. Pearl L.H., and Prodromou C. Structure and mechanism of the Hsp90 molecular chaperone machinery. Annu. Rev. Biochem. 75 (2006) 271-294
67. Petko L., and Lindquist S. Hsp26 is not required for growth at high temperatures, nor for thermotolerance, spore development, or germination. Cell 45 (1986) 885-894
68. Pfund C., Lopez-Hoyo N., Ziegelhoffer T., Schilke B.A., Lopez-Buesa P., Walter W.A., Wiedmann M., and Craig E.A. The molecular chaperone Ssb from Saccharomyces cerevisiae is a component of the ribosome-nascent chain complex. EMBO J. 17 (1998) 3981-3989
69. Picard D. Heat-shock protein 90, a chaperone for folding and regulation. Cell. Mol. Life Sci. 59 (2002) 1640-1648
70. Piper P.W., Ortiz-Calderon C., Holyoak C., Coote P., and Cole M. Hsp30, the integral plasma membrane heat shock protein of Saccharomyces cerevisiae, is a stress-inducible regulator of plasma membrane H(+)-ATPase. Cell Stress Chaperones 2 (1997) 12-24
71. Praekelt U.M., and Meacock P.A. HSP12, a new small heat shock gene of Saccharomyces cerevisiae: analysis of structure, regulation and function. Mol. Gen. Genet. 223 (1990) 97-106
72. Prodromou C., Nuttall J.M., Millson, Roe S.M., Sim T.S., Tan D., Workman P., Pearl L.H., and Piper P.W. Structural basis of the radicicol resistance displayed by a fungal Hsp90. ACS Chem. Biol. (23rd Feb 2009) doi:10.1021/cb9000316 (Epub ahead of print)
73. Prodromou C., Roe S.M., O'Brien R., Ladbury J.E., Piper P.W., and Pearl L.H. Identification and structural characterization of the ATP/ADP-binding site in the Hsp90 molecular chaperone. Cell 90 (1997) 65-75
74. Prodromou C., Siligardi G., O'Brien R., Woolfson D.N., Regan L., Panaretou B., Ladbury J.E., Piper P.W., and Pearl L.H. Regulation of Hsp90 ATPase activity by tetratricopeptide repeat (TPR)-domain co-chaperones. EMBO J. 18 (1999) 754-762
75. Prodromou C., Panaretou B., Chohan S., Siligardi G., O'Brien R., Ladbury J.E., Roe S.M., Piper P.W., and Pearl L.H. The ATPase cycle of Hsp90 drives a molecular 'clamp' via transient dimerization of the N-terminal domains. EMBO J. 19 (2000) 4383-4392
76. Rahman D.R., Bentley N.J., and Tuite M.F. The Saccharomyces cerevisiae small heat shock protein Hsp26 inhibits actin polymerisation. Biochem. Soc. Trans. 23 (1995) 77S
77. Raviol H., Sadlish H., Rodriguez F., Mayer M.P., and Bukau B. Chaperone network in the yeast cytosol: Hsp110 is revealed as an Hsp70 nucleotide exchange factor. EMBO J. 25 (2006) 2510-2518
78. Reading D.S., Hallberg R.L., and Myers A.M. Characterization of the yeast HSP60 gene coding for a mitochondrial assembly factor. Nature 337 (1989) 655-659
79. Regnacq M., and Boucherie H. Isolation and sequence of HSP30, a yeast heat-shock gene coding for a hydrophobic membrane protein. Curr. Genet. 23 (1993) 435-442
80. Roe S.M., Prodromou C., O'Brien R., Ladbury J.E., Piper P.W., and Pearl L.H. Structural basis for inhibition of the Hsp90 molecular chaperone by the antitumor antibiotics radicicol and geldanamycin. J. Med. Chem. 42 (1999) 260-266
81. Rospert S., Glick B.S., Jeno P., Schatz G., Todd M.J., Lorimer G.H., and Viitanen P.V. Identification and functional analysis of chaperonin 10, the groES homolog from yeast mitochondria. Proc. Natl. Acad. Sci. U.S.A. 90 (1993) 10967-10971
82. Sahi C., and Craig E.A. Network of general and specialty J protein chaperones of the yeast cytosol. Proc. Natl. Acad. Sci. U.S.A. 104 (2007) 7163-7168
83. Sanchez Y., Taulien J., Borkovich K.A., and Lindquist S. Hsp104 is required for tolerance to many forms of stress. EMBO J. 11 (1992) 2357-2364
84. Schilke B., Williams B., Knieszner H., Pukszta S., D'Silva P., Craig E.A., and Marszalek J. Evolution of mitochondrial chaperones utilized in Fe-S cluster biogenesis. Curr. Biol. 16 (2006) 1660-1665
85. Schirmer E.C., Glover J.R., Singer M.A., and Lindquist S. HSP100/Clp proteins: a common mechanism explains diverse functions. Trends Biochem. Sci. 21 (1996) 289-296
86. Seymour I.J., and Piper P.W. Stress induction of HSP30, the plasma membrane heat shock protein gene of Saccharomyces cerevisiae, appears not to use known stress-regulated transcription factors. Microbiology 145 Pt 1 (1999) 231-239
87. Shaner L., and Morano K.A. All in the family: atypical Hsp70 chaperones are conserved modulators of Hsp70 activity. Cell Stress Chaperones 12 (2007) 1-8
88. Shaner L., Gibney P.A., and Morano K.A. The Hsp110 protein chaperone Sse1 is required for yeast cell wall integrity and morphogenesis. Curr. Genet. 54 (2008) 1-11
89. Siligardi G., Panaretou B., Meyer P., Singh S., Woolfson D.N., Piper P.W., Pearl L.H., and Prodromou C. Regulation of Hsp90 ATPase activity by the co-chaperone Cdc37p/p50cdc37. J. Biol. Chem. 277 (2002) 20151-20159
90. Smiley J.K., Brown W.C., and Campbell J.L. The 66 kDa component of yeast SFI, stimulatory factor I, is hsp60. Nucleic Acids Res. 20 (1992) 4913-4918
91. Steel G.J., Fullerton D.M., Tyson J.R., and Stirling C.J. Coordinated activation of Hsp70 chaperones. Science 303 (2004) 98-101
92. Tessarz P., Mogk A., and Bukau B. Substrate threading through the central pore of the Hsp104 chaperone as a common mechanism for protein disaggregation and prion propagation. Mol. Microbiol. 68 (2008) 87-97
93. True H.L. The battle of the fold: chaperones take on prions. Trends Genet. 22 (2006) 110-117
94. True H.L., Berlin I., and Lindquist S.L. Epigenetic regulation of translation reveals hidden genetic variation to produce complex traits. Nature 431 (2004) 184-187
95. True H.L., and Lindquist S.L. A yeast prion provides a mechanism for genetic variation and phenotypic diversity. Nature 407 (2000) 477-483
96. Truman A.W., Millson S.H., Nuttall J.M., King V., Mollapour M., Prodromou C., Pearl L.H., and Piper P.W. Expressed in the yeast Saccharomyces cerevisiae, human ERK5 is a client of the Hsp90 chaperone that complements loss of the Slt2p (Mpk1p) cell integrity stress-activated protein kinase. Eukaryot. Cell 5 (2006) 1914-1924
97. Tyson J.R., and Stirling C.J. LHS1 and SIL1 provide a lumenal function that is essential for protein translocation into the endoplasmic reticulum. EMBO J. 19 (2000) 6440-6452
98. Voos W., and Rottgers K. Molecular chaperones as essential mediators of mitochondrial biogenesis. Biochim. Biophys. Acta 1592 (2002) 51-62
99. Walsh P., Bursac D., Law Y.C., Cyr D., and Lithgow T. The J-protein family: modulating protein assembly, disassembly and translocation. EMBO Rep. 5 (2004) 567-571
100. Wandinger S.K., Suhre M.H., Wegele H., and Buchner J. The phosphatase Ppt1 is a dedicated regulator of the molecular chaperone Hsp90. EMBO J. 25 (2006) 367-376
101. Wendler P., Shorter J., Plisson C., Cashikar A.G., Lindquist S., and Saibil H.R. Atypical AAA+ subunit packing creates an expanded cavity for disaggregation by the protein-remodelling factor Hsp104. Cell 31 (2007) 1366-1377
102. Whitesell L., Mimnaugh E.G., De Costa B., Myers C.E., and Neckers L.M. Inhibition of heat shock protein HSP90-pp60v-src heteroprotein complex formation by benzoquinone ansamycins: essential role for stress proteins in oncogenic transformation. Proc. Natl. Acad. Sci. U.S.A. 91 (1994) 8324-8328
103. Wickner R.B., Edskes H.K., Shewmaker F., and Nakayashiki T. Prions of fungi: inherited structures and biological roles. Nat. Rev. Microbiol. 5 (2007) 611-618
104. Zara S., Farris G.A., Budroni M., and Bakalinsky A.T. HSP12 is essential for biofilm formation by a Sardinian wine strain of S. cerevisiae. Yeast 19 (2002) 269-276
105. Zhao R., Davey M., Hsu Y.C., Kaplanek P., Tong A., Parsons A.B., Krogan N., Cagney G., Mai D., Greenblatt J., Boone C., Emili A., and Houry W.A. Navigating the chaperone network: an integrative map of physical and genetic interactions mediated by the hsp90 chaperone. Cell 120 (2005) 715-727