Heat shock 70 kDa protein 1 (HSPA1A) (HSP70)

Heat shock 70 kDa protein 1 (HSP70) is a highly conserved molecular chaperone essential for maintaining cellular protein homeostasis (proteostasis). It functions by binding to nascent or misfolded polypeptides to facilitate correct folding, prevent aggregation, and direct terminally misfolded proteins toward degradation pathways like the ubiquitin-proteasome system (UniProt P0DMV8). In the context of oncology, HSP70 is frequently overexpressed, where it stabilizes oncogenic proteins and inhibits apoptotic signaling, thereby promoting tumor cell survival and resistance to chemotherapy (PubMed: 28810573). Conversely, in neurodegenerative diseases, enhancing HSP70 activity is explored as a strategy to clear toxic protein aggregates such as tau or alpha-synuclein (PubMed: 25685448). Therapeutic strategies targeting HSP70 primarily involve small-molecule inhibitors that bind to its N-terminal ATPase domain or C-terminal substrate-binding domain to disrupt its chaperone cycle (PubChem: 16196824). Despite its potential, the ubiquitous nature of HSP70 presents challenges in achieving selectivity and avoiding systemic toxicity in non-cancerous tissues.

Other names

HSPA1AHSP72HSPA1Heat shock 70 kDa protein 1AHSP70-1Endogenous cellular HSP70

Inhibition of the N-terminal ATPase activity or the C-terminal substrate-binding domain to disrupt the chaperone cycle, leading to the degradation of client proteins and induction of apoptosis.