Dnajc12-flox Mouse

DNAJC12, a co-chaperone, is involved in multiple important biological processes. It is associated with the proper folding of phenylalanine hydroxylase (PAH) together with HSP70 and is involved in monoamine synthesis [2,3]. In the context of diseases, it has implications in pathways related to cancer chemoresistance, neurodegeneration, and hyperphenylalaninemia. Genetic models can be valuable in further exploring its functions.

In breast cancer, DNAJC12 overexpression activates the PI3K-AKT pathway, inhibiting doxorubicin-induced ferroptosis and apoptosis, leading to chemotherapy resistance. Inhibiting AKT or HSP70 can reverse this resistance [1]. In neuroblastoma, down-regulation of DNAJC12 activates glycolysis, increases histone H4K5 lactylation, and up-regulates COL1A1 transcription, promoting tumor progression [4]. In rectal cancer, DNAJC12 up-regulation promotes cell proliferation, migration, and inhibits apoptosis, and it may act through the DNAJC12/HSPA4 axis [5]. In lung cancer, DNAJC12 promotes tumor growth by regulating β-catenin activation, and is activated by HNF1A to enhance aerobic glycolysis and cisplatin resistance [6,7].

In conclusion, DNAJC12 plays essential roles in multiple biological processes, especially in the context of cancer and neurodegenerative diseases. Studies using various models have revealed its significance in processes like chemotherapy resistance, tumorigenesis, and metabolic regulation. These findings provide potential therapeutic targets for treating related diseases.