SDS PAGE of Hsp90 alpha protein.

Hsp90 is a highly conserved and essential stress protein that is expressed in all eukaryotic cells. From a functional perspective, hsp90 participates in the folding, assembly, maturation, and stabilization of specific proteins as an integral component of a chaperone complex (1-4). Despite its label of being a heat-shock protein, hsp90 is one of the most highly expressed proteins in unstressed cells (1–2% of cytosolic protein). It carries out a number of housekeeping functions – including controlling the activity, turnover, and trafficking of a variety of proteins. Most of the hsp90-regulated proteins that have been discovered to date are involved in cell signaling (5-6). The number of proteins now know to interact with Hsp90 is about 100. Target proteins include the kinases v-Src, Wee1, and c-Raf, transcriptional regulators such as p53 and steroid receptors, and the polymerases of the hepatitis B virus and telomerase.5. When bound to ATP, Hsp90 interacts with co-chaperones Cdc37, p23, and an assortment of immunophilin-like proteins, forming a complex that stabilizes and protects target proteins from proteasomal degradation.
In most cases, hsp90-interacting proteins have been shown to co-precipitate with hsp90 when carrying out immunoadsorption studies, and to exist in cytosolic heterocomplexes with it. In a number of cases, variations in hsp90 expression or hsp90 mutation has been shown to degrade signaling function via the protein or to impair a specific function of the protein (such as steroid binding, kinase activity) in vivo. Ansamycin antibiotics, such as geldanamycin and radicicol, inhibit hsp90 function (7).

1. Arlander SJH, et al. (2003) J Biol Chem 278: 52572-52577.
2. Pearl H, et al. (2001) Adv Protein Chem 59:157-186.
3. Neckers L, et al. (2002) Trends Mol Med 8:S55-S61.
4. Pratt W, Toft D. (2003) Exp Biol Med 228:111-133.
5. Pratt W, Toft D. (1997) Endocr Rev 18: 306–360.
6. Pratt WB. (1998) Proc Soc Exptl Biol Med 217: 420–434.
7. Whitesell L, et al. (1994) Proc Natl Acad Sci USA 91: 8324– 8328.

发表文献
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2. Rateb, M.E. et al. (2011). Chaxamycins A–D, Bioactive Ansamycins from a Hyper-arid Desert Streptomyces sp. J. Nat. Prod. 74 (6), 1491-1499. doi:10.1021/np200320u.
 
3. Bartolini, M., Wainer, I.W., Bertucci, C. and Andrisano, V. (2012). The rapid and direct determination of ATPase activity by ion exchange chromatography and the application to the activity of heat shock protein-90. Journal of Pharmaceutical and Biomedical Analysis. 73, 77-81.  doi:10.1016/j.jpba.2012.03.021