Wac, the WW domain-containing coiled-coil adaptor, is primarily associated with transcriptional regulation, autophagy, and mitotic entry [2,3]. It is involved in pathways such as the activation of Polo-like kinase 1 (Plk1) for timely mitotic entry, and in processes like mitophagy-mediated mesenchymal stem cell (MSC) osteogenesis [2,3]. Wac's functions are of great biological importance as it impacts various physiological and pathological processes. Genetic models can be valuable for studying its role.

In osteoporosis, the levels of Wac are diminished in both patients and mouse models. Knockdown of Wac compromises Plk1 activity and delays mitotic entry, while exogenous expression of wild-type Wac can rescue these defects [2,3]. In renal allograft ischemia-reperfusion injury, inhibiting sEV-mediated lncRNA WAC-AS1 (antisense RNA of Wac) secretion can protect against the injury, suggesting a role of the Wac-related lncRNA in this disease condition [1].

In conclusion, Wac plays a crucial role in processes like mitotic entry and MSC osteogenesis. Its dysregulation is associated with diseases such as osteoporosis and renal allograft ischemia-reperfusion injury. The study of Wac using gene-knockout or conditional-knockout mouse models helps to clarify its role in these specific disease areas, providing potential therapeutic targets for treatment.

References:

1. Li, Xinyuan, Peng, Xiang, Zhou, Xiang, He, Weiyang, Gou, Xin. 2023. Small extracellular vesicles delivering lncRNA WAC-AS1 aggravate renal allograft ischemia‒reperfusion injury by inducing ferroptosis propagation. In Cell death and differentiation, 30, 2167-2186. doi:10.1038/s41418-023-01198-x. https://pubmed.ncbi.nlm.nih.gov/37532764/

2. Fan, Shuai, Li, Jinteng, Zheng, Guan, Shen, Huiyong, Ye, Guiwen. 2024. WAC Facilitates Mitophagy-mediated MSC Osteogenesis and New Bone Formation via Protecting PINK1 from Ubiquitination-Dependent Degradation. In Advanced science (Weinheim, Baden-Wurttemberg, Germany), 12, e2404107. doi:10.1002/advs.202404107. https://pubmed.ncbi.nlm.nih.gov/39555688/

3. Qi, Feifei, Chen, Qinfu, Chen, Hongxia, Huang, Jun, Wang, Fangwei. . WAC Promotes Polo-like Kinase 1 Activation for Timely Mitotic Entry. In Cell reports, 24, 546-556. doi:10.1016/j.celrep.2018.06.087. https://pubmed.ncbi.nlm.nih.gov/30021153/