Heat shock protein 70 kilodalton (Hsp70)

Heat shock protein 70 kilodalton (Hsp70) is a highly conserved, ATP-dependent molecular chaperone expressed in nearly all living organisms[1][2][3][4][5][6]. It plays a fundamental role in maintaining proteostasis by assisting in the folding of newly synthesized proteins, refolding of misfolded or aggregated proteins, preventing protein aggregation, and regulating the fate of client proteins under stress conditions[1][2][3][4][5][6]. Structurally, Hsp70 proteins consist of an N-terminal ATPase domain, a peptide substrate-binding domain, and a C-terminal helical lid region[1][2][3][4]. Hsp70 is upregulated in response to various stresses (e.g., heat, oxidative stress, infection), providing cellular protection, but is also implicated in disease processes including cancer, neurodegeneration, cardiovascular disease, and infection[5][6][7]. The human Hsp70 family contains both constitutive (e.g., Hsc70) and inducible forms, which function with co-chaperones such as Hsp40 and CHIP to orchestrate diverse cellular responses[1][2][3][5]. Given its central role in protein quality control and cellular adaptation to stress, Hsp70 is an emerging therapeutic target, particularly in oncology and neurodegenerative disease, with several small molecule inhibitors under development[5][7].

Other names

70-kDa heat shock proteinHsp70 familyHSP70Heat shock cognate 70 (Hsc70)DnaK (bacterial homolog)GRP78 (for ER isoform/BiP, HSPA5)

Inhibition of ATPase activity of Hsp70, disrupting its chaperone function; Disruption of protein folding and refolding; Induction of apoptosis in cancer cells by inhibiting stress protection