Dnajb1, also known as DnaJ homolog subfamily B member 1, is involved in multiple cellular processes. It has been shown to negatively regulate MIG6, a tumor suppressor, promoting epidermal growth factor receptor (EGFR) signaling [6]. Additionally, it destabilizes PDCD5, suppressing p53-mediated apoptosis [7].

In the context of fibrolamellar hepatocellular carcinoma (FLC), Dnajb1 forms a fusion gene with PRKACA (DNAJB1-PRKACA). This fusion transcript is the oncogenic driver in FLC. Peptide-based immunotherapy targeting the DNAJB1-PRKACA fusion protein can induce multifunctional T cells, leading to durable relapse-free survival in a patient [1]. Endogenous CD8 T cell responses to this fusion in FLC patients are rare, but functional fusion-specific T cell receptors (TCRs) have been defined, with one showing strong anti-tumor activity in vivo [2]. The DNAJB1-PRKACA fusion drives FLC through impaired SIK signaling and CRTC2/p300-mediated transcriptional reprogramming [3]. It also regulates LINC00473, which promotes tumor growth and alters mitochondrial fitness in FLC [4,5].

In summary, Dnajb1 has important roles in regulating cell signaling pathways related to tumor suppression and apoptosis. In FLC, the DNAJB1-PRKACA fusion is a key oncogenic driver, and research on this fusion provides insights into the disease mechanism and potential immunotherapeutic strategies. The study of Dnajb1 in the context of FLC using various models helps to understand the disease pathogenesis and develop new treatment options.