Trib2-flox Mouse

TRIB2, a member of the Tribbles pseudokinases family, is a pseudo serine/threonine kinase that functions as a scaffold or adaptor in various physiological and pathological processes. It is involved in multiple signaling pathways, such as the ubiquitin-proteasome system, MAPKK, AKT, and NFκB pathways [2,3,5]. TRIB2 plays a significant role in cell homeostasis, cancer development, and stem cell fate decisions [2,3,5]. Genetic models, like KO/CKO mouse models, are valuable for studying its functions.

In naive T cell homeostasis during aging, TRIB2 is more abundant in naive CD4+ than CD8+ T cells. TRIB2 deficiency increases AKT activity, accelerating proliferation and differentiation in response to interleukin-7 in humans and during lymphopenia in mice. In older adults, the waning of ThPOK and TRIB2 expression in naive CD4+ T cells causes loss of naivety, suggesting TRIB2's key role in regulating T cell homeostasis [1].

In cancer, TRIB2 has potent oncogenic activities in many cancer subtypes, such as melanoma, leukemia, and glioblastoma, and is involved in therapy resistance [2]. For example, in liver cancer cells, TRIB2 desensitizes ferroptosis via βTrCP-mediated TFRC ubiquitination [4]. In gastric cancer with a CIN phenotype, TRIB2 overexpression reduces cell proliferation, colony formation, and cell motility, suggesting a tumor-suppressive function [6].

In conclusion, TRIB2 is crucial for maintaining T cell homeostasis during aging and is significantly involved in cancer development and resistance mechanisms. Gene knockout and conditional knockout mouse models have provided insights into its functions in these biological processes and disease conditions, highlighting its potential as a therapeutic target in relevant diseases.