Heat shock protein 90 alpha family class B member 1 (HSP90AB1)

Heat shock protein 90 alpha family class B member 1 (HSP90AB1), commonly known as HSP90-beta, is a constitutively expressed molecular chaperone that plays a fundamental role in maintaining cellular proteostasis [1, 6]. It facilitates the folding, structural maturation, and stabilization of a diverse set of "client" proteins, including signaling kinases, steroid hormone receptors, and transcription factors [1, 13]. Unlike the inducible alpha isoform, HSP90AB1 is present at high levels under basal conditions and is essential for normal cellular function and development [13, 21]. In many cancers, HSP90AB1 is overexpressed and hijacked to stabilize mutated or overexpressed oncoproteins such as HER2, Akt, and B-Raf, which are critical for tumor survival and proliferation [7, 12]. Consequently, it has become a major therapeutic target, with drugs designed to inhibit its ATPase activity and trigger the proteasomal degradation of its oncogenic clients [9, 15]. Although several HSP90 inhibitors have reached clinical trials, their development has been complicated by dose-limiting toxicities, such as ocular and cardiac side effects, and the induction of a compensatory heat shock response [12, 19]. Current research is exploring isoform-selective inhibitors and combination therapies to enhance efficacy and reduce systemic toxicity [15, 22].

Other names

Heat shock protein 90-betaHSP90BHSPCBHSP84HSPC2Heat shock 84 kDaHeat shock 90kDa protein 1, beta

Inhibition of the N-terminal ATPase activity, which prevents the chaperone cycle and leads to the ubiquitin-mediated proteasomal degradation of client proteins.