Rnf144b, also known as PIR2, is an ubiquitin E3 ligase. It plays diverse roles in multiple biological processes and pathways. It is involved in innate immune responses, spermatogenesis, and is associated with tumorigenesis, sepsis, and antiviral immunity, highlighting its overall biological importance. Genetic models, such as gene knockout (KO) or conditional knockout (CKO) mouse models, are valuable for studying its functions.

In KO mouse models, Rnf144b deficiency greatly promotes IFN production and inhibits EMCV replication in vivo, indicating its role as a negative regulator of innate antiviral response by targeting MDA5 for autophagic degradation [1]. In septic mice with Rnf144b deficiency in myeloid cells, there is higher mortality and exacerbated cardiac dysfunction, showing that Rnf144b alleviates inflammatory responses and cardiac dysfunction in sepsis [2].

In conclusion, Rnf144b is a multifunctional E3 ligase. Through model-based research, its roles in antiviral immunity, sepsis, and potentially in spermatogenesis and tumorigenesis have been revealed. The use of Rnf144b KO/CKO mouse models has contributed significantly to understanding its functions in these disease areas.

References:

1. Li, Guoxiu, Zhang, Jing, Zhao, Zhixun, Tang, Lijie, Lu, Zengjun. 2024. RNF144B negatively regulates antiviral immunity by targeting MDA5 for autophagic degradation. In EMBO reports, 25, 4594-4624. doi:10.1038/s44319-024-00256-w. https://pubmed.ncbi.nlm.nih.gov/39285245/

2. Guo, Rennan, Wang, Jingjing, Tang, Wen, Xiao, Dong. 2023. Rnf144b alleviates the inflammatory responses and cardiac dysfunction in sepsis. In ESC heart failure, 10, 2338-2344. doi:10.1002/ehf2.14383. https://pubmed.ncbi.nlm.nih.gov/37088470/