Dtx3l, also known as B-lymphoma and BAL-associated protein (BBAP), is an E3 ubiquitin ligase. It is involved in multiple cellular pathways, including the interferon-related antiviral response, DNA repair, and cell survival and proliferation regulation. It plays a crucial role in the body's immune defense and cellular homeostasis, and genetic models are valuable for studying its functions [3,4].

In the interferon-induced antiviral response, Dtx3l knockout studies could potentially clarify its role in enhancing the type I interferon antiviral response. It is known to promote the ubiquitination and phosphorylation of TBK1, establishing an IFN-β-ETS1-Dtx3L-TBK1 positive-feedback loop to enhance interferon signaling and inhibit respiratory syncytial virus (RSV) infection [1]. In DNA repair, Dtx3L-mediated TIRR nuclear export and degradation, as seen in over-expression models in prostate cancers, regulates DNA repair pathway choice and PARP inhibitor sensitivity. Decreased TIRR due to Dtx3L overexpression impairs its negative regulation of 53BP1, leading to HR deficiency, chromosomal instability, and increased sensitivity to PARP inhibitors [2].

In conclusion, Dtx3l is essential in the interferon-related antiviral response and DNA repair processes. Model-based research, such as potential Dtx3l knockout or over-expression models, has provided insights into its role in antiviral defense against RSV-related lung diseases and in determining PARP inhibitor sensitivity in prostate cancer. These findings contribute to understanding disease mechanisms and may offer new therapeutic strategies.

References:

1. Huang, Jiaqi, Chen, Zhengrong, Ye, Yunfei, Zhang, Jinping, Hao, Chuangli. 2023. DTX3L Enhances Type I Interferon Antiviral Response by Promoting the Ubiquitination and Phosphorylation of TBK1. In Journal of virology, 97, e0068723. doi:10.1128/jvi.00687-23. https://pubmed.ncbi.nlm.nih.gov/37255478/

2. Ye, Qi, Ma, Jian, Wang, Zixi, Huang, Haojie, Li, Lei. 2024. DTX3L-mediated TIRR nuclear export and degradation regulates DNA repair pathway choice and PARP inhibitor sensitivity. In Nature communications, 15, 10596. doi:10.1038/s41467-024-54978-5. https://pubmed.ncbi.nlm.nih.gov/39632881/

3. Bachmann, Samia B, Frommel, Sandra C, Camicia, Rosalba, Santoro, Raffaella, Hassa, Paul O. 2014. DTX3L and ARTD9 inhibit IRF1 expression and mediate in cooperation with ARTD8 survival and proliferation of metastatic prostate cancer cells. In Molecular cancer, 13, 125. doi:10.1186/1476-4598-13-125. https://pubmed.ncbi.nlm.nih.gov/24886089/

4. Vela-Rodríguez, Carlos, Lehtiö, Lari. . Activities and binding partners of E3 ubiquitin ligase DTX3L and its roles in cancer. In Biochemical Society transactions, 50, 1683-1692. doi:10.1042/BST20220501. https://pubmed.ncbi.nlm.nih.gov/36421918/