Heat shock protein 90 (HSP90) is a member of a family of molecular chaperone proteins which can be upregulated by various stressors including heat stress leading to increases in HSP90 protein expression. Its primary functions include (1) renaturing and denaturing of damaged proteins caused by heat stress and (2) interacting with client proteins to induce cell signaling for gene expression. The latter function is of interest because, in cancer cells, HSP90 has been reported to interact with the transcription hypoxic-inducible factor 1α (HIF1α). In a normoxic environment, HIF1α is degraded and therefore has limited physiological function. In contrast, in a hypoxic environment, stabilized HIF1α acts to promote erythropoiesis and angiogenesis. Since HSP90 interacts with HIF1α, and HSP90 can be upregulated from heat acclimation in humans, we present a proposal that heat acclimation can mimic molecular adaptations to those of altitude exposure. Specifically, we propose that heat acclimation increases HSP90 which then stabilizes HIF1α in a normoxic environment. This has many implications since HIF1α regulates red blood cell and vasculature formation. In this paper we will discuss (1) the functional roles of HSP90 and HIF1α, (2) the interaction between HSP90 and other client proteins including HIF1α, and (3) results from in vitro studies that may suggest how the relationship between HSP90 and HIF1α might be applied to individuals preparing to make altitude sojourns. 1. Introduction Heat shock proteins (HSP’s) are classified as molecular chaperones that play an integral role in the maintenance of damaged cells after heat exposure. When a living organism is exposed to a hyperthermic environment, intracellular HSP expression is increased. A function of HSPs is to sequester and refold denatured proteins [1, 2], with an upregulation protecting cells from future thermal damage [3]. Heat shock protein 90 (HSP90) is a 90？kda protein that has specific functional characteristics when compared to other members of the HSP family. Along with renaturing damaged proteins, HSP90 interacts with target client proteins stimulating the activation of specific signaling transduction pathways [4]. Specifically, in clinical research, HSP90 has been shown to participate in the signaling transduction of some proteins regulating oncogenic factors [5]. Research shows that HSP90 inhibitors have been examined in their role to decrease tumor growth [6] by interacting with hypoxic-inducible factor1α (HIF1α). In this pathway, inhibition of HSP90 leads to less bioavailable HIF1α a transcription
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