Fn3k, short for Fructosamine-3-kinase, is an enzyme that plays a crucial role in protein de-glycation. It mitigates excessive protein glycation by phosphorylating and destabilizing fructosamines, thus preventing the formation of irreversible advanced glycation end-products (AGEs) [2]. This function is related to multiple biological pathways, such as the NRF2-mediated redox balance pathway. NRF2 is a transcription factor controlling a cell stress program implicated in cancer, and its activity depends on Fn3k-mediated de-glycation [1].

In in vivo studies, the development of hepatocellular carcinoma triggered by MYC and Keap1 inactivation was found to depend on Fn3k [1]. This indicates that in the context of this cancer-related pathway, Fn3k is essential for the oncogenic action of NRF2. Without Fn3k, NRF2 is extensively glycated, unstable, and defective in binding to small MAF proteins and transcriptional activation [1].

In conclusion, Fn3k is a key enzyme in protein de-glycation, significantly influencing the NRF2-mediated redox balance pathway. The use of in vivo models, such as those related to hepatocellular carcinoma, has revealed its importance in cancer-associated biological processes, suggesting that Fn3k could be a potential target for cancer therapy [1].

References:

1. Sanghvi, Viraj R, Leibold, Josef, Mina, Marco, Hendrickson, Ronald C, Wendel, Hans-Guido. . The Oncogenic Action of NRF2 Depends on De-glycation by Fructosamine-3-Kinase. In Cell, 178, 807-819.e21. doi:10.1016/j.cell.2019.07.031. https://pubmed.ncbi.nlm.nih.gov/31398338/

2. Ogidigo, Joyce, Kumari, Reena, Sanghvi, Viraj R. 2025. FN3K: the (un)sweetest kinase. In Trends in biochemical sciences, 50, 372-373. doi:10.1016/j.tibs.2025.03.009. https://pubmed.ncbi.nlm.nih.gov/40187910/