Ring1-KO Mouse

Ring1, also known as Ring finger protein 1, is a crucial component of the polycomb-group proteins. It is involved in multiple biological processes, such as chromatin modification as a catalytic subunit within Polycomb repressive complex 1 (PRC1), which catalyzes histone H2A lysine 119 monoubiquitination (H2AK119ub1) [1]. Ring1 has been associated with pathways like Wnt/β-catenin, and is important in processes like neurogenesis, germ-cell-specific transcription, and tumorigenesis [1,2,4]. Gene knockout models can be valuable for studying its functions.

In a neurodevelopment in vitro model, hypomorphic RING1 in PRC1 complexes leads to reduced H2AK119ub1, causing delayed DNA damage repair and cell cycle progression in neural progenitor cells (NPCs), while not significantly impacting NPC differentiation [1]. In pancreatic cancer, UBE2T-mediated ubiquitination of p53 by RING1 confers gemcitabine resistance [3]. In hepatic progenitor cells, overexpression of Ring1 promotes their transformation into cancer stem cells via the Wnt/β-catenin signaling pathway [4]. In tomato plants, the E3 ubiquitin ligase RING1 interacts with COP9 Signalosome Subunit 4 to positively regulate resistance to root-knot nematodes [5].

In conclusion, Ring1 plays essential roles in various biological processes, from neurogenesis to plant defense and tumorigenesis. Findings from gene-based research models, especially in the context of disease-related processes like cancer and in plant-pathogen interactions, highlight its significance. These studies help in understanding the underlying molecular mechanisms and potentially developing targeted interventions.

References:

1. Ryan, C W, Regan, S L, Mills, E F, Srivastava, A, Bielas, S L. 2024. RING1 missense variants reveal sensitivity of DNA damage repair to H2A monoubiquitination dosage during neurogenesis. In Nature communications, 15, 7931. doi:10.1038/s41467-024-52292-8. https://pubmed.ncbi.nlm.nih.gov/39256363/

2. Bajusz, Izabella, Henry, Surya, Sutus, Enikő, Kovács, Gergő, Pirity, Melinda K. 2019. Evolving Role of RING1 and YY1 Binding Protein in the Regulation of Germ-Cell-Specific Transcription. In Genes, 10, . doi:10.3390/genes10110941. https://pubmed.ncbi.nlm.nih.gov/31752312/

3. Jiang, Xiangyan, Ma, Yong, Wang, Tao, Yu, Zeyuan, Jiao, Zuoyi. 2023. Targeting UBE2T Potentiates Gemcitabine Efficacy in Pancreatic Cancer by Regulating Pyrimidine Metabolism and Replication Stress. In Gastroenterology, 164, 1232-1247. doi:10.1053/j.gastro.2023.02.025. https://pubmed.ncbi.nlm.nih.gov/36842710/

4. Zhu, Kai, Li, Jiangwei, Li, Jun, Kong, Guangyao, Li, Zongfang. 2019. Ring1 promotes the transformation of hepatic progenitor cells into cancer stem cells through the Wnt/β-catenin signaling pathway. In Journal of cellular biochemistry, 121, 3941-3951. doi:10.1002/jcb.29496. https://pubmed.ncbi.nlm.nih.gov/31696964/

5. Zou, Jin-Ping, Zhao, Qiu-Feng, Yang, Ting, Ahammed, Golam Jalal, Zhou, Jie. 2022. The E3 ubiquitin ligase RING1 interacts with COP9 Signalosome Subunit 4 to positively regulate resistance to root-knot nematodes in Solanum lycopersicum L. In Plant science : an international journal of experimental plant biology, 322, 111344. doi:10.1016/j.plantsci.2022.111344. https://pubmed.ncbi.nlm.nih.gov/35659944/