Heat shock protein 90-beta (HSP90β)

Heat shock protein 90-beta (HSP90β) is a highly conserved molecular chaperone encoded in humans by the HSP90AB1 gene. It is a cytoplasmic member of the HSP90 family, which stabilizes, folds, and regulates a wide variety of client proteins, many of which are essential for cell proliferation, survival, signal transduction, and stress responses[1][2][7][9]. HSP90β assists in the proper folding and maintenance of newly-synthesized, mutant, misfolded, or denatured proteins under both normal and stress conditions, and promotes the degradation of client proteins that cannot be correctly folded[2][5]. This chaperone is involved in crucial biological functions spanning protein homeostasis, control of the cell cycle, cell signaling, and apoptosis regulation. HSP90β supports the maturation and function of proteins including kinases, transcription factors, hormone receptors, and viral polymerases[9]. It is frequently overexpressed or hyperactive in many cancers and is linked to neurodegenerative, infectious, and inflammatory diseases, making it an attractive but challenging therapeutic target. Inhibitors of HSP90β, such as geldanamycin and its derivatives, function by disrupting its ATPase-dependent chaperone cycle, leading to proteasomal degradation of oncogenic and pro-survival client proteins, but clinical use is hindered by toxicity and resistance concerns[2][5][8][10].

Other names

HSP90betaHSPCBHSP84HSP90AB1HSP90B proteinHSPC2

ATPase inhibition leading to disruption of chaperone cycle and degradation of client proteins; Destabilization and proteasomal degradation of oncogenic/pro-disease proteins; Interference with protein–protein interactions with co-chaperones