Heat-shock protein 90 inhibitors as novel cancer chemotherapeutic agents

Expert Opinion on Emerging Drugs

Volumn 7, Issue 2, 2002, Pages 277-288

  Neckers, Len ^a   Neckers, Katharine ^a  

^a NATIONAL CANCER INSTITUTE   (United States)

Author keywords

Benzoquinone ansamycins; Geldanamycin; Heat shock protein 90; Kinase inhibitors; Molecular chaperones; Moleoalarly targeted therapeutics

Indexed keywords

ANTINEOPLASTIC AGENT; BCR ABL PROTEIN; CHAPERONE; CISPLATIN; DOXORUBICIN; GELDANAMYCIN; HEAT SHOCK PROTEIN 90; HEAT SHOCK PROTEIN 90 INHIBITOR; HYPOXIA INDUCIBLE FACTOR 1ALPHA; IMATINIB; NOVOBIOCIN; PACLITAXEL; PROTEIN INHIBITOR; PROTEIN KINASE B; PROTEIN P53; RADICOL; RAF PROTEIN; RAF1 PROTEIN; UNCLASSIFIED DRUG;

ANTINEOPLASTIC ACTIVITY; APOPTOSIS; BREAST CANCER; CANCER GROWTH; CANCER INHIBITION; CANCER SURVIVAL; CLINICAL TRIAL; COST OF ILLNESS; CYTOSTASIS; DRUG CYTOTOXICITY; DRUG MECHANISM; DRUG POTENTIATION; DRUG TOLERABILITY; HUMAN; LEUKEMIA; LIVER TOXICITY; LYMPHOMA; MOLECULAR STABILITY; NONHUMAN; ONCOGENE NEU; PROSTATE CANCER; REVIEW; SIGNAL TRANSDUCTION;

EID: 0036842742     PISSN: 14728214     EISSN: None     Source Type: Journal    
DOI: 10.1517/14728214.7.2.277     Document Type: Review

References (92)

1. Jacobsohn VA: Novel therapeutics for the treatment of graft versus host disease. Expert Opin. Investig. Drugs (2002) 11(9):1271-1280.
2. Garber K: Rapamycin's resurrection: A new way to target the cancer cell cycle. J. Natl. Cancer Inst. (2001) 93(20):1517-1519.
3. La Rosee P, O'Dwyer ME, Druker BJ: Insights from preclinical studies for new combination treatment regimens with the Bcr-Abl kinase inhibitor imatinib mesylate (Gleevec/Glivec) in chronic myelogenous leukaemia: A translational perspective. Leukemia (2002) 16(7):1213-1219.
4. Yufu Y, Nishimura J, Nawata H: High constitutive expression of heat-shock protein 90 alpha in human acute leukaemia cells. Leuk. Res. (1992) 16(6-7):597-605.
5. Oppermann H, Levinson AD, Levintow L, Varmus HE, Bishop JM, Kawai S: Two cellular proteins that immunoprecipitate with the transforming protein of Rous sarcoma virus. Virology (1992) 113(2):736-751. First paper to describe association of Hsp90 with a kinase.
6. Ziemiecki A, Catelli MG, Joab I, Moncharmont B: Association of the heat-shock protein hsp90 with steroid hormone receptors and tyrosine kinase oncogene products. Biochem. Biophys. Res. Commun. (1986) 138(3):1298-1307. Description of Hsp90 association with steroid receptors.
7. Xu Y, Lindquist S: Heat-shock protein hsp90 governs the activity of pp60v-src kinase. Proc. Natl. Acad. Sci. USA. (1993) 90(15):7074-7078.
8. Stancato LF, Silverstein AM, Owens-Grillo JK, Chow YH, Jove R, Pratt WB: The hsp90-binding antibiotic geldanamycin decreases Raf levels and epidermal growth factor signalling without disrupting formation of signalling complexes or reducing the specific enzymatic activity of Raf kinase. J. Biol. Chem. (1997) 272(7):4013-4020.
9. Srivastava PK, Maki RG: Stress-induced proteins in immune response to cancer. Curr. Top. Microbiol. Immunol. (1991) 167:109-123.
10. Ciocca DR, Fuqua SA, Lock-Lim S, Toft DO, Welch WJ, McGuire W: Response of human breast cancer cells to heat shock and chemotherapeutic drugs. Cancer Res. (1992) 52(13):3648-3654.
11. Whitesell L, Shifrin SD, Schwab G, Neckers L: Benzoquinonoid ansamycins possess selective tumouricidal activity unrelated to src kinase inhibition. Cancer Res. (1992) 52(7):1721-1728.
12. Whitesell L, Mimnaugh EG, De Costa B, Myers CE, Neckers LM: 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. USA (1994) 91(18):8324-8328. First paper to identify Hsp90 as the molecular target of benzoquinone ansamycins.
13. Ferrarini M, Heltai S, Zocchi MR, Rugarli C: Unusual expression and localization of heat-shock proteins in human tumour cells. Int. J. Cancer (1992) 51(4):613-619.
14. Blagosklonny MV, Toretsky J, Bohen S, Neckers L: Mutant conformation of p53 translated in vitro or in vivo requires functional HSP90. Proc. Natl. Acad. Sci. USA. (1996) 93(16):8379-8383.
15. Sato S, Fujita N, Tsuruo T: Moduiation of Akt kinase activity by binding to Hsp90. Proc. Natl. Acad. Sci. USA. (2000) 97(20):10832-10837.
16. Hostein I, Robetson D, Distefano F, Workman P, Clarke PA: Inhibition of signal transduction by the Hsp90 inhibitor 17-allylamino-17-demethoxygeldanamycin results in cytostasis and apoptosis. Cancer Res. (2001) 6(10):4003-4009.
17. Schulte TW, Blagosklonny MV, Romanova L et al.: Destabilization of Raf-1 by geldanamycin leads to disruption of the Raf-1-MEK-mitogen-activated protein kinase signalling pathway. Mol. Cell Biol. (1996) 16(10):5839-5845.
18. An WG, Schulte TW, Neckers LM: The heat-shock protein 90 antagonist geldanamycin alters chaperone association with p210bcr-abl and v-src proteins before their degradation by the proteasome. Cell Growth Differ. (2000) 11(7):355-360. This and the following paper describe the dependence of Bcr-Abl kinase on Hsp90 for stability and function.
19. Shiotsu Y, Neckers LM, Wortman I et al.: Novel oxime derivatives of radicicol induce erythroid differentiation associated with preferential G(1) phase accumulation against chronic myelogenous leukaemia cells through destabilization of Bcr-Abl with Hsp90 complex. Blood (2000) 96(6):2284-2291.
20. Bonvini P, Gastaldi T, Falini B, Rosolen A: Nucleophosmin-anaplastic lymphoma kinase (NPM-ALK), a novel Hsp90-client tyrosine kinase: Downregulation of NPM-ALK expression and tyrosine phosphorylation in ALK(+) CD30(+) lymphoma cells by the Hsp90 antagonist 17-allylamino17-demethoxygeldanamycin. Cancer Res. (2002) 62(5):1559-1566.
21. Miller P, Schnur RC, Barbacci E, Moyer MP, Moyer JD: Binding of benzoquinoid ansamycins to p100 correlates with their ability to deplete the erbB2 gene product p185. Biochem. Biophys. Res. Commun. (1994) 201(3):1313-1319. This and the following two papers document the Hsp90 dependence of ErbB2 (Her-2/Neu) tyrosine kinase.
22. Miller P, Diorio C, Moyer M et al.: Depletion of the erbB-2 gene product p185 by benzoquinoid ansamycins. Cancer Res. (1994) 54(10):2724-2730.
23. Chavany C, Mimnaugh E, Miller P et al.: p185erbB2 binds to GRP94 in vivo. Dissociation of the p 185erbB2/GRP94 heterocomplex by benzoquinone ansamycins precedes depletion of p 185erbB2. J. Biol. Chem. (1996) 271(9):4974-4977.
24. Stepanova L, Leng X, Parker SB, Harper JW. Mammalian p50Cdc37 is a protein kinase-targeting subunit of Hsp90 that binds and stabilizes Cdk4. Genes Dev. (1996) 10(12):1491-1502. Describes the involvement of p50Cdc37 in Hsp90 complexes that associate with kinases.
25. Aligue R, Akhavan-Niak H, Russell P: A role for Hsp90 in cell cycle control: Weel tyrosine kinase activity requires interaction with Hsp90. EMBO J. (1994) 13(24):6099-6106.
26. Minet E, Mottet D, Michel G et al.: Hypoxia-induced activation of HIF-1: Role of HIF-lalpha-Hsp90 interaction. FEBS Lett. (1999) 460(2):251-256.
27. Isaacs JS, Jung YJ, Mimnaugh EG, Martinez A, Cutyitta F, Neckers LM: Hsp90 regulates a VHL-independent HIF-1alpha degradative pathway. J. Biol. Chem. (2002) 277(33):29936-29944.
28. Fang Y, Fliss AE, Robins DM, Caplan A: Hsp90 regulates androgen receptor hormone binding affinity in vivo. J. Biol. Chem. (1996) 271(45):28697-28702.
29. Pratt WB, Toft DO: Steroid receptor interactions with heat-shock protein and immunophilin chaperones. Endocr. Rev. (1997) 18(3):306-360. An excellent review of the interaction of steroid hormone receptors with molecular chaperones.
30. Segnitz B, Gehring U: The function of steroid hormone receptors is inhibited by the hsp90-specific compound geldanamycin. J. Biol. Chem. (1997) 272(30):18694-18701.
31. Bagatell R, Khan O, Paine-Murrieta G, Taylor CW, Akinaga S, Whitesell L: Destabilization of steroid receptors by heat-shock protein 90-binding drugs: A ligand-independent approach to hormonal therapy of breast cancer. Clin. Cancer Res. (2001) 7(7):2076-2084.
32. Haendler B, Schuttke I, Schleuning WD: Androgen receptor signalling: Comparative analysis of androgen response elements and implication of heat-shock protein 90 and 14-3-3eta. Mol. Cell Endocrinol. (2001) 173(1-2):63-73.
33. Holt SE, Aisner DL, Baur J et al.: Functional requirement of p23 and Hsp90 in telomerase complexes. Genes Dev. (1999) 13(7):817-826.
34. Grenert JP, Sullivan WP, Fadden P et al.: The amino-terminal domain of heat-shock protein 90 (hsp90) that binds geldanamycin is an ATP/ADP switch domain that regulates hsp90 conformation. J. Biol. Chem. (1997) 272(38):23843-23850. This and the following two papers identify the GA binding site on Hsp90 to be an amino terminal nucleotide-binding pocket that regulates Hsp90 conformation.
35. Stebbins CE, Russo AA, Schneider C, Rosen N, Hartl FU, Pavletich NP: Crystal structure of an Hsp90-geldanamycin complex: Targeting of a protein chaperone by an antitumour agent. Cell (1997) 89(2):239-250.
36. Prodromou C, Roe SM, O'Brien R, Ladbury JE, Piper PW, Pearl LH: Identification and structural characterization of the ATP/ADP-binding site in the Hsp90 molecular chaperone. Cell (1997) 90(1):65-75.
37. Csermely P, Kajtar J, Hollosi M et al.: ATP induces a conformational change of the 90-kDa heat-shock protein (hsp90). J. Biol. Chem. (1993) 268(3):1901-1907. An early paper suggesting that Hsp90 binds ATP and that this has consequences for chaperone function.
38. Panaretou B, Prodromou C, Roe SM et al.: ATP binding and hydrolysis are essential to the function of the Hsp90 molecular chaperone in vivo. EMBO J. (1998) 17(16):4829-4836.
39. Grenert JP, Johnson BD, Toft DO: The importance of ATP binding and hydrolysis by hsp90 in formation and function of protein heterocomplexes. J. Biol. Chem. (1999) 274(25):17525-17533.
40. Scheibel T, Buchner J: The Hsp90 complex-a super-chaperone machine as a novel drug target. Biochem. Pharmacol. (1998) 56(6):675-682. A nice review of the mechanisms of the Hsp90 chaperone machine.
41. Hernandez MP, Chadli A, Toft DO: HSP40 binding is the first step in the HSP90 chaperoning pathway for the progesterone receptor. J. Biol. Chem. (2002) 277(14):11873-11881.
42. Hernandez MP, Sullivan WP, Toft DO: The assembly and intermolecular properties of the hsp70-Hop-hsp90 molecular chaperone complex. J. Biol. Chem. (2002) 277(41):38294-38304.
43. Young JC, Hartl FU: Polypeptide release by Hsp90 involves ATP hydrolysis and is enhanced by the cochaperone p23. EMBO J. (2000) 19(21):5930-5940.
44. Siligardi G, Panaretou B, Meyer P et al.: Regulation of Hsp90 ATPase activity by the cochaperone Cdc37p/p50cdc37. J. Biol. Chem. (2002) 277(23):20151-20159.
45. McLaughlin SH, Smith HW, Jackson SE: Stimulation of the weak ATPase activity of human hsp90 by a client protein. J. Mol. Biol. (2002) 315(4):787-798.
46. Schneider C, Sepp-Lorenzino L, Nimmesgern E et al.: Pharmacologic shifting of a balance between protein refolding and degradation mediated by Hsp90. Proc. Natl. Acad. Sci. USA (1996) 93(25):14536-14541. The first paper to suggest that Hsp90 can promote both the stability and the degradation of its client proteins and that GA shifts this balance towards degradation.
47. Connell P, Ballinger CA, Jiang J et al.: The cochaperone CHIP regulates protein triage decisions mediated by heat-shock proteins. Nat. Cell Biol. (2001) 3(1):93-96. Identification of the first chaperone-dependent E3 ubiquitin ligase.
48. Meacham GC, Patterson C, Zhang W, Younger JM, Cyr DM: The Hsc70 cochaperone CHIP targets immature CFTR for proteasomal degradation. Nat. Cell Biol. (2001) 3(1):100-105.
49. Xu W, Marcu M, Yuan X, Mimnaugh E, Patterson C, Neckers L: Chaperone-dependent E3 ubiquitin ligase CHIP mediates a novel degradative pathway for c-ErbB2/Neu. Proc. Natl. Acad. Sci. USA (2002) 99(20):12847-12852. Demonstration that CHIP can cooperate with GA to promote degradation of ErbB2,
50. Chiosis G, Rosen N, Sepp-Lorenzino L: LY-294002-geldanamycin heterodimers as selective inhibitors of the PI3K and PI3K-related family. Bioorg. Med. Chem. Lett. (2001) 11(7):909-913.
51. Schulte TW, Neckers LM: The benzoquinone ansamycin 17-allylamino-17-demethoxygeldanamycin binds to HSP90 and shares important biologic activities with geldanamycin. Cancer Chemother. Pharmacol. (1998) 42(4):273-279. A paper showing that the clinically tolerable GA derivative, 17-AAG, binds to Hsp90 and has activity similar to that of GA.
52. Kelland LR, Sharp SY, Rogers PM, Myers TG, Workman P: DT-Diaphorase expression and tumour cell sensitivity to 17-allylamino, 17-demethoxygeldanamycin, an inhibitor of heat-shock protein 90. J. Natl. Cancer Inst. (1999) 91(22):1940-1949.
53. Agnew EB, Wilson RH, Grem JL, Neckers L, Bi D, Takimoto CH: Measurement of the novel antitumour agent 17-(allylamino)-17-demethoxygeldanamycin in human plasma by high-performance liquid chromatography. J. Chromatogr. B Biomed. Sci. Appl. (2001) 755(1-2):237-243.
54. Srethapakdi M, Liu F, Tavorath R, Rosen N: Inhibition of Hsp90 function by ansamycins causes retinoblastoma gene product-dependent G1 arrest. Cancer Res. (2000) 60(14):3940-3946.
55. Blagosklonny MV, Fojo T, Bhalla KN et al.: The Hsp90 inhibitor geldanamycin selectively sensitizes Bcr-Abl-expressing leukaemia cells to cytotoxic chemotherapy. Leukaemia (2001) 15(10):1537-1543.
56. Nimmanapalli R, O'Bryan E, Bhalla K: Geldanamycin and its analogue 17-allylamino-17-demethoxygeldanamycin lowers Bcr-Abl levels and induces apoptosis and differentiation of Bcr-Abl-positive human leukemic blasts. Cancer Res. (2001) 61(5):1799-1804.
57. Gorre ME, Ellwood-Yen K, Chiosis G, Rosen N, Sawyers CL: BCR-ABL point mutants isolated from patients with STI571-resistant chronic myeloid leukaemia remain sensitive to inhibitors of the BCR-ABL chaperone heat-shock protein 90. Blood (2002) 100(8):3041-3044. A paper showing that Gleevec-resistant Bcr-Abl protein remains sensitive to 17-AAG.
58. Solit D et al.: 17-Allyl-amino-geldanamycin induces the degradation of AR and HER2 in prostate cancer xenograft tumours and inhibits their growth. Proceedings of the AACR (2001) 42:363.
59. Gorre ME, Mohammed M, Ellwood K et al.: Clinical resistance to STI-571 cancer therapy caused by BCR-ABL gene mutation or amplification. Science (2001) 293(5531):876-880.
60. Munster PN, Basso A, Solit D, Norton L, Rosen N: Modulation of Hsp90 Function by Ansamycins Sensitizes Breast Cancer Cells to Chemotherapy-Induced Apoptosis in an RB- and Schedule-Dependent Manner. See: E. A. Sausville, Combining cytotoxics and 17-allylamino, 17-demethoxygeldanamycin: Sequence and tumour biology matters, Clin. Cancer Res, (2001) 7:2155-2158. Clin. Cancer Res. (2001) 7(8):2228-2236.
61. Munster PN, Basso A, Solit D, Norton L, Rosen N: Modulation of Hsp90 Function by Ansamycins Sensitizes Breast Cancer Cells to Chemotherapy-Induced Apoptosis in an RB- and Schedule-Dependent Manner. See: E. A. Sausville, Combining cytotoxics and 17-allylamino, 17-demethoxygeldanamycin: Sequence and tumour biology matters, Clin. Cancer Res, (2001) 7:2155-2158. Clin. Cancer Res. (2001) 7(8):2228-2236.
62. Munster PN, Basso A, Solit D, Norton L, Rosen N: Modulation of Hsp90 Function by Ansamycins Sensitizes Breast Cancer Cells to Chemotherapy-Induced Apoptosis in an RB- and Schedule-Dependent Manner. See: E. A. Sausville, Combining cytotoxics and 17-allylamino, 17-demethoxygeldanamycin: sequence and tumour biology matters, Clin. Cancer Res, (2001) 7:2155-2158. Clin. Cancer Res. (2001) 7(8):2228-2236.
63. Nguyen DM, Lorang D, Chen GA, Stewart JH 4th, Tabibi E, Schrump DS: Enhancement of paclitaxel-mediated cytotoxicity in lung cancer cells by 17-allylamino geldanamycin: In vitro and in vivo analysis. Ann. Thorac. Surg. (2001) 72(2):371-378.
64. Nguyen DM, Chen A, Mixon A, Schrump DS: Sequence-dependent enhancement of paclitaxel toxicity in non-small cell lung cancer by 17-allylamino 17-demethoxygeldanamycin. J. Thorac. Cardiovasc. Surg. 118(5):908-915.
65. Horowitz JM, Park SH, Bogenmann E et al.: (1990) Frequent inactivation of the retinoblastoma antioncogene is restricted to a subset of human tumour cells. Proc. Natl. Acad. Sci. USA (1999) 87(7):2775-2779.
66. Lai SL, Brauch H, Knutsen T et al.: Molecular genetic characterization of neuroendocrine lung cancer cell lines. Anti Cancer Res. (1995) 15(2):225-232.
67. Zhong H, DE Marzo AM, LAUGHNER E et al.: Overexpression of hypoxia-inducible factor-1alpha in common human cancers and their metastases. Cancer Res. (1999) 59(22):5830-5835.
68. Kurose K, Zhou XP, Araki T, Cannistra SA, Maher ER, Eng C: Frequent loss of PTEN expression is linked to elevated phosphorylated Akt levels but not associated with p27 and cyclin D1 expression, in primary epithelial ovarian carcinomas, Am. J. Pathol (2001) 158(6):2097-2106.
69. Sharma SV, Agatsuma T, Nakano H: Targeting of the protein chaperone, HSP90, by the transformation suppressing agent, radicicol. Oncogene (1998) 16(20):2639-2645. This and the following two papers demonstrate that radicicol also binds to the amino terminal nucleotide pocket in Hsp90 and has biologic activity similar to GA.
70. Schulte TW, Akinaga S, Soga S et al.: Antibiotic radicicol binds to the N-terminal domain of Hsp90 and shares important biologic activities with geldanamycin. Cell Stress Chaperones (1998) 3(2):100-108.
71. Roe SM, Prodromou C, O'Brien R, Ladbury JE, Piper PW, Pearl LH: Structural basis for inhibition of the Hsp90 molecular chaperone by the antitumour antibiotics radicicol and geldanamycin. J. Med. Chem. (1999) 42(2):260-266.
72. Marcu MG, Chadli A, Bouhouche I, Catelli M, Neckers LM: The heat-shock protein 90 antagonist novobiocin interacts with a previously unrecognized ATP-binding domain in the carboxyl terminus of the chaperone. J. Biol. Chem. (2000) 275(47):37181-37186. This and the following paper describe a novel ATP binding site in the C-terminus of Hsp90 as the binding site for a third class of Hsp90 inhibitor, novobiocin.
73. Marcu MG, Schulte TW, Neckers L: Novobiocin and related coumarins and depletion of heat-shock protein 90- dependent signalling proteins. J. Natl. Cancer Inst. (2000) 92(3):242-248.
74. Chiosis G, Timaul MN, Lucas B et al.: A small molecule designed to bind to the adenine nucleotide pocket of Hsp90 causes Her2 degradation and the growth arrest and differentiation of breast cancer cells. Chem. Biol. (2001) 8(3):289-299.
75. Johnson BD, Chadli A, Felts SJ, Bouhouche I, Catelli MG, Toft DO: Hsp90 chaperone activity requires the full-length protein and interaction among its multiple domains. J. Biol. Chem. (2000) 275(42):32499-32507.
76. Pearl LH, Prodromou C: Structure and in vivo function of Hsp90. Curr. Opin. Struct. Biol. (2000) 10(1):46-51.
77. Pearl LH, Prodromou C: Structure, function and mechanism of the Hsp90 molecular chaperone. Adv. Protein Protdn Chem. (2001) 59:157-186
78. Owen BA, Sullivan WP, Felts SJ, Toft DO: Regulation of heat-shock protein 90 ATPase activity by sequences in the carboxyl terminus. J. Biol. Chem. (2002) 277(9):7086-7091.
79. Soti C, Racz A, Csermely P: A nucleotide-dependent molecular switch controls ATP binding at the C-terminal domain of Hsp90. N-terminal nucleotide binding unmasks a C-terminal binding pocket. J. Biol. Chem. (2002) 277(9):7066-7075. A further analysis of the C-terminal ATP binding domain of Hsp90.
80. Itoh H, Ogura M, Komatsuda A, Wakui H, Miura AB, Tashima Y: A novel chaperone-activity-reducing mechanism of the 90-kDa molecular chaperone HSP90. Biochem. J. (1999) 343:697-703.
81. Slepian MJ, Massia SP, Whitesell L: Preconditioning of smooth muscle cells via induction of the heat shock response limits proliferation following mechanical injury. Biochem. Biophys. Res. Commun. (1996) 225(2):600-607.
82. Conde AG, Lau SS, Dillmann WH, Mestril R: Induction of heat-shock proteins by tyrosine kinase inhibitors in rat cardiomyocytes and myogenic cells confers protection against simulated ischaemia. J. Mol. Cell Cardiol. (1997) 29(7):1927-1938.
83. Ali A, Bharadwa J S, O'Carroll R, Ovsenek N: HSP90 interacts with and regulates the activity of heat shock factor 1 in Xenopus oocytes. Mol. Cell. Biol. (1998) 18(9):4949-4960.
84. Kim HR, Kang HS, Kim HD: Geldanamycin induces heat-shock protein expression through activation of HSF1 in K562 erythroleukemic cells. IUBMB Life. (1999) 48(4):429-433.
85. Xiao N, Callaway CW, Lipinski CA, Hicks SD, Defranco DB: Geldanamycin provides post-treatment protection against glutamate-induced oxidative toxicity in a mouse hippocampal cell line. J. Neurochem. (1999) 72(1):95-101.
86. Guo Y, Guettouche T, Fenna M et al.: Evidence for a mechanism of repression of heat shock factor 1 transcriptional activity by a multichaperone complex. J. Biol. Chem. (2001) 276(49):45791-45799.
87. Lu A, Ran R, Parmentier-Batteur S, Nee A, Sharp FR: Geldanamycin induces heat-shock proteins in brain and protects against focal cerebral ischaemia. J. Neurochem. (2002) 81(2):355-364.
88. Bagatell R, Paine-Murrieta GD, Taylor CW et al.: Induction of a heat shock factor 1-dependent stress response alters the cytotoxic activity of hsp90-binding agents. Clin. Cancer Res. (2000) 6(8):3312-3318.
89. Rutherford SL, Lindquist S: Hsp90 as a capacitor for morphological evolution. Nature (1998) 396(6709):336-342. This and the following paper present evidence supporting the hypothesis that Hsp90 may play a role in evolution.
90. Queitsch C, Sangster TA, Lindquist S: Hsp90 as a capacitor of phenotypic variation. Nature (2002) 417(6889):618-624.
91. Mimnaugh EG, Worland PJ, Whitesell L, Neckers LM: Possible role for serine/threonine phosphorylation in the regulation of the heteroprotein complex between the hsp90 stress protein and the pp60v-src tyrosine kinase. J. Biol. Chem. (1995) 270(48):28654-28659.
92. Zhao YG, Gilmore R, Leone G, Coffey MC, Weber B, Lee PW: Hsp90 phosphorylation is linked to its chaperoning function. Assembly of the reovirus cell attachment protein. J. Biol. Chem. (2001) 276(35):32822-32827.