Rnf181, a RING finger protein, functions as an E3 ubiquitin ligase. It is involved in multiple biological pathways, such as Hippo/YAP signaling, ERα signaling, and antigen receptor signaling to NF-κB. It plays a role in processes like cell proliferation, migration, and invasion, and is also associated with diseases including breast cancer, coronary artery disease, and lymphoma [1,2,4].

In triple negative breast cancer (TNBC), Rnf181 depletion significantly inhibited cell migration, invasion, and proliferation, as YAP protein level and Hippo signaling target genes decreased. YAP overexpression could rescue these effects. Rnf181 interacted with YAP and promoted its stability by inhibiting K48-linked poly-ubiquitination of YAP [1]. In ERα positive breast cancer, Rnf181 depletion inhibited cancer progression in vivo and in vitro, reduced ERα protein level and its target gene expression. It associated with ERα and might promote its stability via inducing ERα K63-linked poly-ubiquitination [2]. In coronary artery disease, Rnf181 was identified as a potential biomarker through weighted gene co-expression network analysis, and its expression was validated in cardiotoxicity mouse models, CAD patient cohort, and GWAS [3]. In lymphoma, Rnf181 functioned as an E3 ubiquitin ligase to inhibit antigen receptor signaling to NF-κB downstream of CARD11, and limited the proliferation of human diffuse large B cell lymphoma cells [4].

In conclusion, Rnf181 is a key regulator in multiple biological processes and disease conditions. Through gene knockout or depletion studies in cell lines and animal models, its roles in cancer progression, especially in breast cancer, and in coronary artery disease and lymphoma have been revealed. These findings provide insights into the underlying mechanisms of these diseases and potential therapeutic targets related to Rnf181.

References:

1. Zhou, Rui, Ding, Yinlu, Xue, Min, Xiong, Bin, Zhuang, Ting. 2020. RNF181 modulates Hippo signaling and triple negative breast cancer progression. In Cancer cell international, 20, 291. doi:10.1186/s12935-020-01397-3. https://pubmed.ncbi.nlm.nih.gov/32655323/

2. Zhu, Jian, Li, Xin, Su, Peng, Zang, Yifeng, Ding, Yinlu. 2020. The ubiquitin ligase RNF181 stabilizes ERα and modulates breast cancer progression. In Oncogene, 39, 6776-6788. doi:10.1038/s41388-020-01464-z. https://pubmed.ncbi.nlm.nih.gov/32973333/

3. Dang, Ruoyu, Qu, Bojian, Guo, Kaimin, Lin, Jianping, Hu, Yunhui. 2022. Weighted Co-Expression Network Analysis Identifies RNF181 as a Causal Gene of Coronary Artery Disease. In Frontiers in genetics, 12, 818813. doi:10.3389/fgene.2021.818813. https://pubmed.ncbi.nlm.nih.gov/35222523/

4. Pedersen, Sarah M, Chan, Waipan, Jattani, Rakhi P, Mackie, deMauri S, Pomerantz, Joel L. 2015. Negative Regulation of CARD11 Signaling and Lymphoma Cell Survival by the E3 Ubiquitin Ligase RNF181. In Molecular and cellular biology, 36, 794-808. doi:10.1128/MCB.00876-15. https://pubmed.ncbi.nlm.nih.gov/26711259/