DnaJ heat shock protein family (Hsp40) member B1 messenger RNA (DNAJB1 mRNA)

DnaJ heat shock protein family (Hsp40) member B1 (DNAJB1) mRNA is the messenger RNA encoding the DNAJB1 protein, a critical co-chaperone that regulates the Hsp70 chaperone system (Source 3.4.2). DNAJB1 contains a highly conserved J-domain that interacts with Hsp70 to stimulate its ATPase activity, thereby facilitating the folding, transport, and degradation of client proteins (Source 1.1.3). In clinical oncology, the most prominent therapeutic target involving this mRNA is the DNAJB1-PRKACA fusion transcript, which is the pathognomonic driver of fibrolamellar carcinoma (FLC) (Source 3.1.2). This fusion results from a ~400 kb deletion on chromosome 19, creating a chimeric mRNA that encodes a protein with the J-domain of DNAJB1 fused to the catalytic domain of protein kinase A (PRKACA) (Source 4.2.4). Therapeutic approaches targeting this mRNA include the development of siRNA and antisense oligonucleotides (ASOs) to selectively reduce its expression, as well as neoantigen-based vaccines like Fusion-VAC-XS15 that target the resulting fusion protein (Source 4.2.1, 3.1.3). Beyond FLC, dysregulation of DNAJB1 mRNA and other J-domain family members like DNAJB6 is associated with various cancers and neurodegenerative disorders, where they play a role in managing misfolded protein aggregates like alpha-synuclein and huntingtin (Source 4.3.5).

Other names

Hsp40 mRNADNAJ1 mRNAHDJ1 mRNADnaJ homolog subfamily B member 1 mRNADNAJB1-PRKACA fusion transcriptJ-domain protein transcript

RNA interference, Antisense inhibition, Neoantigen-based immunotherapy