Appbp2-flox Mouse

Appbp2, amyloid protein-binding protein 2, is involved in the ubiquitin-proteasome system as a substrate receptor of the Cullin 2-RING ligase (CRL2) complex. It determines the specificity of protein degradation by recognizing C-degrons in substrates for ubiquitin-mediated proteolysis [3]. APPBP2 is associated with multiple biological pathways and has significant biological importance in processes like adipose tissue regulation, cell proliferation, and senescence. Genetic models, such as KO/CKO mouse models, are valuable for studying its functions.

In adipose tissues, the CUL2-APPBP2 ubiquitin E3 ligase complex determines the stability of PRDM16 protein. Inhibition of CUL2-APPBP2 extends the half-life of PRDM16, promoting beige adipocyte biogenesis. In contrast, elevated CUL2-APPBP2 in aged adipose tissues degrades PRDM16, repressing adipocyte thermogenesis. Adipocyte-specific deletion of CUL2-APPBP2 counteracts diet-induced obesity, glucose intolerance, insulin resistance, and dyslipidaemia in mice [1]. In human mesenchymal stem cells (hMSCs), CUL2, through APPBP2, targets and promotes the ubiquitin-proteasome-mediated degradation of TSPYL2, a negative regulator of proliferation. This in turn down-regulates the aging marker P21waf1/cip1, counteracting hMSC senescence [2].

In conclusion, Appbp2 is crucial in the ubiquitin-proteasome-mediated protein degradation process. Its function in adipose tissue regulation, as revealed by mouse models, has implications for metabolic diseases such as obesity, glucose intolerance, insulin resistance, and dyslipidaemia. In addition, its role in hMSC senescence provides a molecular basis for interventions against aging-related diseases.