Heat shock 70 kDa protein (HSP70) (HSP70)

Heat shock 70 kDa protein (HSP70) is a ubiquitous molecular chaperone that plays a fundamental role in maintaining cellular proteostasis by assisting in the folding of nascent proteins and the refolding of misfolded polypeptides (UniProt P0DMV8). It functions through an ATP-dependent cycle where the hydrolysis of ATP triggers conformational changes that allow the protein to bind and release hydrophobic segments of client proteins (PubMed: 28553442). In the context of immunotherapy, recombinant HSP70 is utilized as an exogenous chaperone or adjuvant to enhance the immune response against specific antigens, particularly in cancer vaccines (PubMed: 16110651). It achieves this by binding to receptors such as CD91 and Toll-like receptors (TLR2/4) on antigen-presenting cells, which facilitates antigen cross-presentation and the activation of innate immune signaling (PubMed: 12496977). Beyond its use as a therapeutic agent, HSP70 is a significant drug target in oncology, as its overexpression is linked to tumor cell survival, resistance to chemotherapy, and inhibition of apoptosis (PubMed: 25100735).

Other names

HSPA1AHSP72Heat shock 70 kDa protein 1HSPA1HSP70-1HSP70.1HSP70-1A

HSP70 acts as a molecular chaperone by binding to hydrophobic regions of unfolded proteins in an ATP-dependent manner to prevent aggregation and facilitate proper folding (PubMed: 28553442). As an exogenous adjuvant, it interacts with receptors like CD91 and Toll-like receptors (TLR2/4) on dendritic cells to promote antigen uptake, maturation, and cross-presentation to T cells (PubMed: 16110651, PubMed: 12496977). Small molecule inhibitors typically target the ATP-binding site or the substrate-binding domain to disrupt these chaperone functions, leading to the degradation of client proteins and induction of apoptosis in cancer cells (PubMed: 25100735).