Heat shock 70 kDa protein 4 (HSPA4) (HSPA4)

Heat shock 70 kDa protein 4 (HSPA4), also known as APG-2, is a molecular chaperone belonging to the Hsp110/Hsp70 family (UniProt P34932). It plays a vital role in cellular proteostasis by assisting in protein folding, preventing aggregation, and facilitating the degradation of misfolded proteins (NCBI Gene 3308). In various cancers, such as colorectal cancer and leukemia, HSPA4 is frequently overexpressed and acts as a survival factor by stabilizing oncogenic client proteins and inhibiting apoptosis (PMID: 31435447). Targeting HSPA4 mRNA through RNA interference (RNAi) or antisense oligonucleotides (ASOs) aims to reduce the levels of this chaperone, thereby sensitizing tumor cells to stress and chemotherapy (PMID: 28656233). While specific clinical inhibitors for HSPA4 are currently in the experimental stage, it remains a significant target for therapeutic intervention and a potential biomarker for disease progression and prognosis. The molecule's involvement in the inflammatory response and its role as a co-chaperone further highlight its importance in maintaining cellular integrity under pathological conditions. Therapeutic challenges include the high sequence homology among Hsp70 family members, which complicates the development of isoform-specific inhibitors. Despite these challenges, HSPA4 remains a promising candidate for precision medicine in oncology.

Other names

APG-2HSP70RYhsp70-like protein 1Heat shock 70-related protein APG-2HSP70L1

RNA interference (RNAi) or antisense-mediated degradation of HSPA4 mRNA to prevent protein translation, or direct inhibition of the HSPA4 protein's ATPase activity to disrupt chaperone function.