DnaJ heat shock protein family (Hsp40) (Hsp40)

The DnaJ heat shock protein family (Hsp40) consists of a large group of molecular chaperones defined by a conserved J-domain that interacts with Hsp70 [10, 11]. These proteins are essential for cellular proteostasis, assisting in protein folding, assembly, and the prevention of toxic aggregation by stimulating the ATPase activity of Hsp70 [1, 10]. In oncology, various Hsp40 members are frequently overexpressed, where they stabilize oncoproteins and promote tumor cell survival and chemoresistance [2, 12]. Conversely, in neurodegenerative diseases like Parkinson's and Alzheimer's, Hsp40 proteins play a protective role by preventing the accumulation of misfolded protein aggregates [7, 11]. Therapeutic development focuses on small-molecule inhibitors to target specific Hsp40 isoforms in cancer or activators to enhance their chaperone function in neurodegeneration [2, 11]. For instance, DNAJA1 has been identified as a potential target for anti-tumor therapy due to its role in stabilizing mutant p53 [2]. However, the high degree of homology among the 41 human family members presents significant challenges for achieving selectivity and avoiding systemic toxicity [10, 15]. Despite these challenges, Hsp40 remains a promising target for precision medicine given its specific roles in various disease pathologies [6, 13].

Other names

Heat shock protein 40Hsp40J-domain proteinJ-proteinChaperone DnaJ

Stimulation of Hsp70 ATPase activity to facilitate protein folding and prevent aggregation; therapeutic inhibitors block this interaction to destabilize oncoproteins in cancer.