Vcpip1-KO Mouse

Vcpip1, also known as valosin-containing protein-interacting protein 1, is a deubiquitinating enzyme. It is involved in multiple biological processes, such as post-mitotic Golgi cisternae reassembly and maintenance in interphase through its interaction with P97/VCP [1]. It also participates in regulating NF-κB signaling pathways, DNA-protein crosslink repair, and is related to hepatitis B virus (HBV) life cycle [2,3,4].

In macrophages, Vcpip1 deficiency reduces Erbin expression, increases NF-κB phosphorylation, and promotes the release of inflammatory factors, indicating its negative regulation of NF-κB signaling pathways [2]. In HBV-related studies, Vcpip1 binds to HBx, stabilizes it, and upregulates HBV transcription, antigen expression, and genome replication, establishing it as a multi-functional positive regulator of HBV [3]. In the context of DNA-protein crosslink repair, Vcpip1 knockout mice are prone to genomic instability and premature aging, as Vcpip1 is phosphorylated and activated by ATM/ATR in response to DPC induction, then deubiquitinates SPRTN to promote its chromatin relocalization [4].

In conclusion, Vcpip1 plays essential roles in multiple biological processes. Its deficiency in relevant models reveals its significance in inflammatory response regulation, HBV-related diseases, and DNA-protein crosslink repair-associated aging-related conditions. These findings help in understanding the underlying molecular mechanisms and may provide potential targets for related disease treatment.

References:

1. Liao, Tianzhui, Li, Ruotong, Lu, Ping, Gao, Haishan, Li, Faxiang. 2024. Molecular Basis of VCPIP1 and P97/VCP Interaction Reveals Its Functions in Post-Mitotic Golgi Reassembly. In Advanced science (Weinheim, Baden-Wurttemberg, Germany), 11, e2403417. doi:10.1002/advs.202403417. https://pubmed.ncbi.nlm.nih.gov/39234822/

2. Zuo, Jing, Wu, Die, Zhang, Ying, Wu, Xiaojing, Song, Xuemin. 2024. VCPIP1 negatively regulates NF-κB signaling pathways by deubiquitinating and stabilizing Erbin in MDP-stimulated macrophages. In International immunopharmacology, 143, 113622. doi:10.1016/j.intimp.2024.113622. https://pubmed.ncbi.nlm.nih.gov/39550842/

3. Kang, Ning, Liu, Nannan, Liu, Mu, Shen, Zhongliang, Liu, Jing. 2024. Identification and characterization of host factor VCPIP1 as a multi-functional positive regulator of hepatitis B virus. In Journal of virology, 98, e0158124. doi:10.1128/jvi.01581-24. https://pubmed.ncbi.nlm.nih.gov/39494904/

4. Huang, Jinzhou, Zhou, Qin, Gao, Ming, Machida, Yuichi, Lou, Zhenkun. 2020. Tandem Deubiquitination and Acetylation of SPRTN Promotes DNA-Protein Crosslink Repair and Protects against Aging. In Molecular cell, 79, 824-835.e5. doi:10.1016/j.molcel.2020.06.027. https://pubmed.ncbi.nlm.nih.gov/32649882/