J-domain protein (JDP) (JDP)

J-domain proteins (JDPs), also known as Hsp40 proteins, are a large and diverse family of molecular cochaperones characterized by a conserved ~70 amino acid J-domain. Their primary function is to regulate the activity of Hsp70 chaperones by stimulating their ATPase activity, which facilitates the capture and folding of client proteins [Kampinga & Craig, 2010, Nature Reviews Molecular Cell Biology]. JDPs play a critical role in protein quality control, preventing the accumulation of misfolded proteins and assisting in the disassembly of protein aggregates [Jiang et al., 2007, Science]. In disease contexts, JDPs are implicated in various cancers where they may promote tumor cell survival, and in neurodegenerative disorders like Parkinson's and Huntington's disease, where their dysfunction contributes to toxic protein aggregation [Mayer & Bukau, 2005, Nature]. Furthermore, certain JDPs are essential for the replication of viruses, such as HIV and Hepatitis C, making them attractive targets for antiviral therapy [Taguwa et al., 2015, Cell Host & Microbe]. Therapeutic strategies targeting JDPs often involve small molecules that disrupt the J-domain's interaction with Hsp70 or inhibit the JDP's ability to stimulate Hsp70, thereby modulating the chaperone network to treat protein-misfolding diseases or cancer [Wisen et al., 2008, ACS Chemical Biology].

Other names

DnaJ proteinHsp40Heat shock protein 40J-proteinCochaperone

Inhibition of J-domain-mediated stimulation of Hsp70 ATPase activity and disruption of the Hsp70-JDP interaction interface.