Map4k1-flox Mouse

Map4k1, also known as HPK1 (Hematopoietic Progenitor Kinase1), is a serine/threonine Ste20-related protein kinase. It acts as an intracellular negative regulator, mainly in hematopoietic lineage cells, regulating T cells, B cells, dendritic cells, etc. It is involved in multiple pathways, such as TCR and BCR signaling, cytokine-cytokine receptor interactions, chemokine signaling, and the PI3K-AKT pathway. It also plays a role in immunity and cancer-related processes [2,3,4,6].

In glioblastoma, MAP4K1 silencing inhibited GBM cell proliferation and glioma growth, and its deficiency abolished GBM cell pro-proliferation responses to IL-18, suggesting an oncogenic role via the intrinsic IL-18/IL-18R pathway [1]. In MAP4K1KO mice, tumors grew slower, and infiltrating T cells were less exhausted and more active and proliferative, indicating its role in T cell-mediated anti-tumor immunity [2]. In AML, overexpression of MAP4K1 in AML cells induced resistance to Homoharringtonine, and it was an independent risk factor predicting poor prognosis, modulating cell cycle through MAPK and DNA damage/repair pathways [5].

In conclusion, Map4k1 is a key regulator in both immunity and cancer-related processes. Gene knockout mouse models have revealed its role in promoting tumor growth in glioblastoma and AML, as well as its negative regulation of T cell function. Understanding Map4k1 function provides potential therapeutic targets for cancer immunotherapy and treatment of AML.