Naa40-flox Mouse

Naa40, or N-alpha-acetyltransferase 40, is a highly specific epigenetic enzyme. It catalyzes the transfer of an acetyl moiety to the alpha -amino group of serine 1 on histones H4 and H2A, thus playing a role in epigenetic regulation [1,3,6]. This histone N -terminal acetylation is involved in various cellular processes, including gene expression control, chromatin function, and is associated with conditions like cancer, metabolic disorders [2,7].

Depletion of Naa40 in murine hepatocytes leads to increased intracellular acetyl -CoA levels and enhanced lipid synthesis, as well as impaired insulin signalling [2]. In colorectal cancer (CRC) cells, Naa40 depletion inhibits cell proliferation and survival, increases sensitivity to 5 -Fluorouracil treatment, and delays the growth of xenograft tumors. It also reduces symmetric dimethylation of histone H4 by downregulating PRMT5, altering the expression of oncogenes and tumor suppressor genes [1]. In CRC, Naa40 controls key one -carbon metabolic genes, promotes resistance to antimetabolite chemotherapy, and its expression is associated with TYMS levels and 5 -FU response [3]. In osteosarcoma, Naa40 depletion reduces cell viability, migration, and invasion, and Naa40 contributes to tumor development by regulating AGR2 expression epigenetically [5]. In HCT116 and HT -29 colorectal cancer cells, Naa40 depletion enhances apoptosis via the mitochondrial caspase -9 -mediated apoptotic cascade in a p53 -independent manner [6].

In conclusion, Naa40 is crucial for maintaining normal cellular functions, especially in processes related to metabolism and cancer. Through gene knockout -like experiments in cells and animal models, its role in promoting cancer cell growth, metabolic regulation, and apoptosis inhibition has been revealed, making it a potential therapeutic target for cancers such as colorectal cancer, liver cancer, and osteosarcoma [1,3,4,5,6].