Heat shock 70 kDa protein family (Hsp70)

The Heat shock 70 kDa protein (Hsp70) family consists of highly conserved molecular chaperones essential for maintaining cellular proteostasis by assisting in protein folding, refolding of misfolded proteins, and directing damaged proteins for degradation (UniProt, 2023). These proteins operate through an ATP-dependent cycle, alternating between a high-affinity ADP-bound state and a low-affinity ATP-bound state to interact with hydrophobic segments of client polypeptides (PubMed, PMID: 30236539). In oncology, Hsp70 is frequently overexpressed, providing a survival advantage to malignant cells by stabilizing oncoproteins and suppressing apoptotic pathways, which has led to the development of Hsp70 inhibitors as potential anti-cancer agents (NCBI, NBK562241). In contrast, for neurodegenerative conditions like Alzheimer's and Parkinson's diseases, Hsp70 is targeted to facilitate the clearance of toxic protein aggregates such as tau or alpha-synuclein (PubMed, PMID: 28851105). Therapeutic strategies include small molecules that target the N-terminal nucleotide-binding domain or the C-terminal substrate-binding domain to modulate chaperone activity (PubChem, 2024).

Other names

70 kilodalton heat shock proteinsHSPA familyDnaK homologsMolecular chaperone Hsp70HSPA1AHSPA8Hsc70

Inhibition of the N-terminal ATPase domain to prevent ATP hydrolysis and substrate release, or disruption of the interaction between Hsp70 and its co-chaperones (e.g., BAG3, HSP40) to promote the degradation of client proteins (PubMed, PMID: 25683110, PMID: 31430120).