Heat shock protein 90 beta isoform (HSP90β)

Heat shock protein 90 beta isoform (HSP90β) is a constitutively expressed molecular chaperone that plays a crucial role in maintaining cellular proteostasis by assisting the folding, maturation, and stabilization of a large array of client proteins, many of which are essential for cell signaling, proliferation, and survival[1][2][3][5][6][7]. HSP90β is one of four human HSP90 isoforms (along with HSP90α, GRP94, and TRAP1) and is predominantly found in the cytoplasm where it is vital under normal conditions, whereas other isoforms are stress-inducible or compartment-localized[5][6]. HSP90β’s chaperoning activity depends on ATP binding and hydrolysis, enabling conformational changes that regulate its interaction with client proteins, including kinases, steroid hormone receptors, and transcription factors[2][3]. Overexpression or hyperactivation of HSP90β supports the stability of numerous oncogenic proteins, making it a critical driver in tumorigenesis and an important therapeutic target in cancer as well as inflammation and neurodegenerative conditions[3][5][6][7]. Multiple drugs targeting HSP90β or pan-HSP90 inhibitors have entered clinical trials, though selectivity and toxicity remain major challenges for their therapeutic application[5][6][7].

Other names

HSP90 betaHSP90BHSP90βHSPCBHeat shock protein 90 kDa beta member 1HSP90B1

ATP-competitive inhibition of HSP90’s N-terminal domain, preventing chaperone activity and leading to degradation of client proteins Disruption of HSP90-client protein complexes, facilitating proteasomal degradation Inhibition of downstream signaling pathways essential for cancer cell survival