Heat shock 70 kDa protein 1 (Hsp70-1) (Hsp70-1)

Heat shock 70 kDa protein 1 (Hsp70-1) is a major stress-inducible molecular chaperone that maintains cellular proteostasis by assisting in protein folding and preventing aggregation (UniProt P0DMV8). It consists of an N-terminal nucleotide-binding domain (NBD) with ATPase activity and a C-terminal substrate-binding domain (SBD) (PubMed: 29434345). In cancer, Hsp70-1 is often overexpressed, where it inhibits apoptosis and promotes tumor cell survival and metastasis, making it a significant therapeutic target (PubMed: 30241310). Conversely, its role in neurodegenerative diseases involves the failure to prevent the accumulation of toxic protein aggregates, suggesting that its activation could be beneficial in those contexts (PubMed: 28211448). Pharmacological targeting of Hsp70-1 primarily involves small molecules that inhibit its ATPase cycle or disrupt its interaction with co-chaperones (PubMed: 25654565).

Other names

HSPA1AHSPA1BHSP70-1HSP72Hsp70.1Heat shock 70 kDa protein 1AHeat shock 70 kDa protein 1B

Inhibition of the N-terminal nucleotide-binding domain (NBD) to block ATPase activity or the C-terminal substrate-binding domain (SBD) to prevent client protein interaction, leading to proteotoxic stress and apoptosis (PubMed: 29434345).