Heat shock cognate 71 kDa protein (HSPA8) (HSPA8)

Heat shock cognate 71 kDa protein (HSPA8), also known as HSC70, is a constitutively expressed member of the Hsp70 family of molecular chaperones (UniProt P11142). Unlike the stress-induced Hsp70, HSPA8 is essential for basal cellular proteostasis, performing critical tasks such as the folding of nascent polypeptides and the ATP-dependent uncoating of clathrin-coated vesicles (PubMed: 19114711). It is a central component of chaperone-mediated autophagy (CMA), where it recognizes and transports substrate proteins containing a KFERQ-like motif to lysosomes for degradation (PubMed: 25213453). In oncology, HSPA8 is frequently overexpressed, contributing to the stability of oncoproteins and the survival of cancer cells under metabolic stress. It also plays a significant role in autoimmune diseases like systemic lupus erythematosus, where its modulation by the peptide drug Lupuzor (P140) alters antigen presentation (PubMed: 26306650). Therapeutic development focuses on inhibiting its ATPase domain or disrupting its interaction with co-chaperones, though achieving selectivity over other Hsp70 isoforms remains a primary challenge (PubMed: 21830225).

Other names

HSC70Heat shock 70 kDa protein 8HSP71HSC71Lipopolysaccharide-associated protein 1 (LAP-1)N-myristoyltransferase inhibitor protein 71

Inhibition of the N-terminal ATPase domain to prevent chaperone-assisted protein folding; modulation of chaperone-mediated autophagy (CMA) to alter lysosomal degradation of autoantigens or oncoproteins.