HSP90 is an abundantly and ubiquitously expressed heat shock protein. It is understood to exist in two principal forms α and β, which share 85% sequence amino acid homology. The two isoforms of Hsp90, are expressed in the cytosolic compartment (1).   Despite the similarities, HSP90α exists predominantly as a homodimer while HSP90β exists mainly as a monomer.(2) From a functional perspective, hsp90 participates in the folding, assembly, maturation, and stabilization of specific proteins as an integral component of a chaperone complex. (3-6)  Furthermore, Hsp90 is highly conserved between species; having 60% and 78% amino acid similarity between mammalian and the corresponding yeast and Drosophila proteins, respectively.

Hsp90 is a highly conserved and essential stress protein that is expressed in all eukaryotic cells. Despite it’s label of being a heat-shock protein, hsp90 is one of the most highly expressed proteins in unstressed cells (12% 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. (7-8). 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 (9).