Heat shock protein 90-alpha; Heat shock protein 90-beta (HSP90α; HSP90β)

Heat shock protein 90-alpha/beta are highly conserved, abundant cytosolic molecular chaperones essential for maintaining cellular proteostasis. They assist folding, maturation, stabilization, and degradation of a wide range of proteins called “clients” – many of which are involved in cell signaling, proliferation, differentiation, and survival. HSP90 is ATP-dependent, cycling between open and closed conformations to facilitate client interactions. The alpha isoform (HSP90α) is inducible under stress, while the beta isoform (HSP90β) is constitutively expressed. Both are heavily investigated as oncology drug targets because many oncoproteins (kinases, hormone receptors) require Hsp90 chaperoning for stability, and tumor cells often show high Hsp90 expression. HSP90 also has known roles in neurodegenerative disease and infection. Multiple drugs target its ATP-binding pocket, leading to client protein degradation and tumor cell death, but safety remains a challenge due to the broad physiological roles of Hsp90.

Other names

Hsp90HSP90HSP90AA1 (alpha, inducible)HSP90AB1 (beta, constitutive)90 kDa heat shock proteinheat shock protein 90HSP90AHSP90B

Competitive inhibition of ATPase activity at the N-terminal domain of Hsp90 (prevents its chaperone function, causes degradation of client proteins) Disruption of chaperone cycle leading to proteasomal degradation of oncoproteins