DnaJ heat shock protein family member B4 (DNAJB4)

DnaJ heat shock protein family member B4 (DNAJB4) is a molecular chaperone and co-chaperone in the HSP40 family, primarily responsible for recognizing misfolded proteins and recruiting them to HSP70 for ATP-dependent refolding or degradation[1][2]. DNAJB4 plays an essential role in the maintenance of protein homeostasis, especially in muscle tissue where its deficiency leads to muscle weakness, protein aggregation, and respiratory failure. It binds the cell adhesion protein E-cadherin, facilitates proper protein folding, and also participates in targeting misfolded E-cadherin for degradation[2]. DNAJB4 acts as a tumor suppressor, with its decreased expression associated with colorectal carcinoma and poorer patient outcomes[2]. DNAJB4 is highly conserved and ubiquitously expressed, with critical functions in muscle contractility and cellular stress defense[1]. Its expression can be pharmacologically upregulated by HSP90 inhibitors, suggesting avenues for cancer therapy and possibly chaperonopathy intervention[3]. Currently, there are no direct drugs targeting DNAJB4, but its expression pattern makes it a candidate biomarker for muscle disease and certain cancers. Loss of function mutations in DNAJB4 cause congenital myopathy with early respiratory failure, and its functional impairment leads to pathological protein aggregation in muscle cells[1][2].

Other names

DnaJ homolog subfamily B member 4DNAJB4DNAJWHLJ1HSP40 homologHeat shock protein 40 homologHeat shock 40 kDa protein 1 homologHuman liver DnaJ-like proteinCMYO21CMYP21DjB4DnaJ-like heat shock protein 40

Upregulation via HSP90 inhibition: Increased DNAJB4 expression by blocking HSP90, stimulates proteostasis. No approved drugs with antagonism, agonism, or direct modulation described.