Fbxl16-flox Mouse

Fbxl16, or F-box and leucine-rich repeat protein 16, is an essential component of the E3 ubiquitin ligases. E3 ubiquitin ligases are involved in regulating a wide range of life activities such as cell cycle, proliferation, and apoptosis [1,2,3,4,5,6]. It participates in multiple pathways including the PP2AB55α /Cyclin D1 axis, AKT1/GSK3β/cyclin D1 pathway, SRC-3-AKT signaling pathway, and the IRS1/AKT signaling pathway, and is thus of great biological importance in understanding cellular functions and disease mechanisms [1,3,4].

In a brain-specific conditional knockout (cko) FBXL16 mouse model, it was found that FBXL16 could be a new regulator of Alzheimer's disease (AD). Its deficiency led to reduced degradation of amyloid precursor protein (APP), increased neuroinflammation, and cognitive impairments, indicating its role in promoting APP degradation and improving cognitive function in AD [2]. In breast cancer cells, FBXL16 silencing inhibited cell growth, increased apoptosis and autophagy, suggesting that FBXL16 aggravates malignant behaviors in breast cancer via the SRC-3-AKT signaling pathway [3]. In lung adenocarcinomas with KRAS mutation, FBXL16 depletion enhanced sensitivity to the KRASG12C inhibitor, highlighting its potential as a therapeutic target [4].

In conclusion, Fbxl16 is crucial in regulating various biological processes related to cell growth, apoptosis, and protein degradation. Studies using gene knockout models, especially the CKO mouse model in AD research, have revealed its significant roles in specific disease areas such as Alzheimer's disease, breast cancer, and lung adenocarcinoma with KRAS mutation. These findings provide a basis for further exploring its potential as a therapeutic target in these diseases.