RNF34, a Ring-finger-containing protein, functions as an E3 ubiquitin ligase. It is involved in multiple biological pathways, including those related to inflammation, immunity, metabolism, and cerebrovascular regulation [1,3,4]. In the context of these pathways, it plays a crucial role in processes like inflammasome activity regulation, antiviral immunity, and energy metabolism regulation. Genetic models, such as gene knockout (KO) mouse models, have been instrumental in studying RNF34.

In KO mouse models, global RNF34 knockout substantially promoted angiotensin II-induced middle cerebral artery remodeling, hypertension, and neurological dysfunction. Specifically, smooth muscle cell (SMC) RNF34 expression was found to be a critical regulator of hypertension and MCA remodeling. Loss of RNF34 enhanced AngII-induced mouse brain vascular SMCs proliferation, migration, and invasion, via increased NADPH-derived ROS generation due to reduced p22phox ubiquitin-dependent degradation [2].

In conclusion, RNF34 is a key E3 ubiquitin ligase with diverse functions in biological processes. Model-based research, especially through RNF34 KO mouse models, has revealed its significant role in cerebrovascular-related diseases like hypertension. These findings contribute to understanding the mechanisms underlying these diseases and may provide potential therapeutic targets.

References:

1. Li, Xue, Jiang, Quan, Song, Guiyu, Pober, Jordan S, Jane-Wit, Dan. 2023. A ZFYVE21-Rubicon-RNF34 signaling complex promotes endosome-associated inflammasome activity in endothelial cells. In Nature communications, 14, 3002. doi:10.1038/s41467-023-38684-2. https://pubmed.ncbi.nlm.nih.gov/37225719/

2. Fang, Shaokuan, Cheng, Yingying, Deng, Fang, Zhang, Beilin. 2021. RNF34 ablation promotes cerebrovascular remodeling and hypertension by increasing NADPH-derived ROS generation. In Neurobiology of disease, 156, 105396. doi:10.1016/j.nbd.2021.105396. https://pubmed.ncbi.nlm.nih.gov/34015492/

3. He, Xiang, Zhu, Yongjie, Zhang, Yanhong, Wei, Congwen, Zhong, Hui. 2019. RNF34 functions in immunity and selective mitophagy by targeting MAVS for autophagic degradation. In The EMBO journal, 38, e100978. doi:10.15252/embj.2018100978. https://pubmed.ncbi.nlm.nih.gov/31304625/

4. Wei, Ping, Pan, Dongning, Mao, Chunxiao, Wang, Yong-Xu. 2011. RNF34 is a cold-regulated E3 ubiquitin ligase for PGC-1α and modulates brown fat cell metabolism. In Molecular and cellular biology, 32, 266-75. doi:10.1128/MCB.05674-11. https://pubmed.ncbi.nlm.nih.gov/22064484/