Rnf144a, a member of the RING-in-between RING (RBR) E3 ubiquitin ligase family, plays diverse and crucial roles in multiple biological processes. It is involved in pathways related to innate immune responses, autophagy, and cancer-related cellular behaviors. Genetic models, such as gene knockout (KO) mouse models, are valuable for studying its functions [1,2,3].

In KO mouse models, Rnf144a deficiency impairs DNA virus-or cytosolic DNA-triggered innate immune signaling, indicating its role as a positive regulator in these pathways [1]. Rnf144a-deficient mice are more prone to carcinogen-induced bladder tumorigenesis, as the loss of Rnf144a promotes the stabilization of PD-L1 and other proteins like DNA-PKcs and BMI1 [2]. Also, Rnf144a-deficient mice are protected from L. monocytogenes infection due to inhibited autophagy-related functions of Rnf144a [3].

In conclusion, Rnf144a is essential for proper innate immune responses against DNA viruses, as well as for suppressing tumorigenesis in the context of bladder cancer. Its role in inhibiting autophagy during L. monocytogenes infection further highlights its significance in host-pathogen interactions. The study of Rnf144a using KO mouse models has provided valuable insights into these disease-related biological processes.

References:

1. Yang, Bo, Pei, Jinyong, Lu, Chen, Wang, Hui, Wang, Jie. 2023. RNF144A promotes antiviral responses by modulating STING ubiquitination. In EMBO reports, 24, e57528. doi:10.15252/embr.202357528. https://pubmed.ncbi.nlm.nih.gov/37955227/

2. Ho, Shiuh-Rong, Lee, Yu-Cheng, Ittmann, Michael M, Chan, Keith Syson, Lin, Weei-Chin. 2021. RNF144A deficiency promotes PD-L1 protein stabilization and carcinogen-induced bladder tumorigenesis. In Cancer letters, 520, 344-360. doi:10.1016/j.canlet.2021.08.008. https://pubmed.ncbi.nlm.nih.gov/34400221/

3. Yang, Bo, Shen, Mengyang, Lu, Chen, Wang, Hui, Wang, Jie. 2024. RNF144A inhibits autophagy by targeting BECN1 for degradation during L. monocytogenes infection. In Autophagy, 21, 789-806. doi:10.1080/15548627.2024.2429380. https://pubmed.ncbi.nlm.nih.gov/39608349/