Cop1-flox Mouse

Cop1, also known as RFWD2, is an E3 ubiquitin ligase. It plays a vital role in multiple biological processes, including cell proliferation, apoptosis, DNA repair, and is involved in various signaling pathways [3]. In plants, it is crucial for light signal transduction and photomorphogenic development, while in mammals, it is a regulator of tumorigenesis and metabolism [4]. Genetic models, such as KO mouse models, have been instrumental in studying its functions.

In triple-negative breast cancer (TNBC) mouse models, deletion of Cop1 in cancer cells reduces secretion of macrophage-associated chemokines, decreases tumor macrophage infiltration, enhances anti-tumor immunity, and strengthens the immune checkpoint blockade (ICB) response. Mechanistically, Cop1 functions through proteasomal degradation of the C/ebpδ protein, with Trib2 acting as a scaffold for this process [1]. In microglia, Cop1-deficient mouse models show that in the absence of Cop1, c/EBPβ accumulates, driving a pro-inflammatory and neurodegeneration-related gene program, and accelerating tau-mediated neurodegeneration [2].

In conclusion, Cop1 is an essential E3 ubiquitin ligase involved in multiple biological functions. Through KO mouse models, its role in cancer immunotherapy, such as in TNBC, and in neurodegeneration, like in Alzheimer's disease-related microglia activation, has been revealed. These findings provide potential therapeutic targets for improving cancer immunotherapy efficacy and treating neurodegenerative diseases.