C57BL/6NCya-Rnf125em1flox/Cya
Common Name:
Rnf125-flox
Product ID:
S-CKO-13807
Background:
C57BL/6NCya
Product Type
Age
Genotype
Sex
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Basic Information
Strain Name
Rnf125-flox
Strain ID
CKOCMP-67664-Rnf125-B6N-VA
Gene Name
Product ID
S-CKO-13807
Gene Alias
4930553F04Rik; C730049O14Rik
Background
C57BL/6NCya
NCBI ID
Modification
Conditional knockout
Chromosome
18
Phenotype
Document
Application
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Note: When using this mouse strain in a publication, please cite “C57BL/6NCya-Rnf125em1flox/Cya mice (Catalog S-CKO-13807) were purchased from Cyagen.”
Strain Description
Ensembl Number
ENSMUST00000050004
NCBI RefSeq
NM_026301
Target Region
Exon 3
Size of Effective Region
~0.6 kb
Detailed Document
Overview of Gene Research
Rnf125, also known as Ring Finger Protein 125, is an E3 ubiquitin ligase. Ubiquitin ligases play crucial roles in regulating protein degradation, which in turn impacts various biological pathways and processes. Rnf125 is involved in multiple pathways such as the SRSF1-ERK, Wnt/β-catenin, and antiviral innate immune response pathways, highlighting its importance in cell growth, inflammation, and immune regulation [1,3,4]. Genetic models, especially gene knockout (KO) and conditional knockout (CKO) mouse models, can be valuable for studying its functions in vivo.
In hepatocellular carcinoma (HCC), Rnf125 was found to be downregulated in tumour tissues, and its overexpression inhibited HCC proliferation and metastasis both in vitro and in vivo. Mechanistically, it interacts with SRSF1 and accelerates its proteasome-mediated degradation, impeding HCC progression by inhibiting the ERK signalling pathway [1].
In the context of endotoxemia, Rnf125 is an E3 ubiquitin ligase that initiates K63-linked ubiquitination of the NLRP3 leucine-rich repeat domain, and together with Cbl-b, sequentially ubiquitinates NLRP3, limiting inflammasome activation and endotoxemia [2].
In osteoarthritis (OA), adenovirus-mediated overexpression of Rnf125 inhibited the degradation of the extracellular matrix of chondrocytes induced by IL-1β. NFATC2 binds to the Rnf125 promoter and directly regulates its transcription, and Rnf125 leads to the ubiquitination and degradation of TRIM14, suppressing the Wnt/β-catenin signalling pathway [3].
In the antiviral innate immune response, CD97 upregulates Rnf125 expression to induce Rnf125-mediated RIG-I degradation via K48-linked ubiquitination, inhibiting virus-induced type-I interferon release and enhancing RNA virus replication [4].
In HCC, Rnf125-mediated ubiquitination of MCM6 regulates the proliferation of human liver HCC cells [5].
In cancer immunotherapy-related studies, Rnf125 interacts with PD-L1, promotes its K48-linked polyubiquitination and degradation, and in tumour-bearing mice, Rnf125 knockout led to higher PD-L1 levels and faster tumour growth, while overexpression had the opposite effect [6].
In asthma, Rnf125 was downregulated in the bronchial epithelium, and its hypermethylation promoted autophagy-induced oxidative stress by increasing HMGB1 stability [7].
Rnf125 also physically interacts with p53, ubiquitinates it, and targets it for proteasome degradation, negatively regulating p53 functions [8].
In head and neck squamous cell carcinoma (HNSCC), Rnf125 overexpression inhibited immune escape by promoting PD-L1 ubiquitinational degradation [9].
In conclusion, Rnf125 is a key E3 ubiquitin ligase involved in diverse biological processes. Model-based research, especially through KO/CKO mouse models, has revealed its significance in diseases like HCC, endotoxemia, OA, antiviral immune response, asthma, and cancers related to immune escape. Understanding Rnf125's functions provides potential therapeutic targets for these diseases.
References:
1. Feng, Zhigang, Ke, Shanjia, Wang, Chaoqun, Wu, Yaohua, Ma, Yong. 2023. RNF125 attenuates hepatocellular carcinoma progression by downregulating SRSF1-ERK pathway. In Oncogene, 42, 2017-2030. doi:10.1038/s41388-023-02710-w. https://pubmed.ncbi.nlm.nih.gov/37142680/
2. Tang, Juan, Tu, Sha, Lin, Guoxin, Lipkowitz, Stanley, Zhang, Jian. . Sequential ubiquitination of NLRP3 by RNF125 and Cbl-b limits inflammasome activation and endotoxemia. In The Journal of experimental medicine, 217, . doi:10.1084/jem.20182091. https://pubmed.ncbi.nlm.nih.gov/31999304/
3. Lv, Runxiao, Du, Lili, Bai, Lunhao. 2023. RNF125, transcriptionally regulated by NFATC2, alleviates osteoarthritis via inhibiting the Wnt/β-catenin signaling pathway through degrading TRIM14. In International immunopharmacology, 125, 111191. doi:10.1016/j.intimp.2023.111191. https://pubmed.ncbi.nlm.nih.gov/37951197/
4. Chang, Huasong, Hou, Peili, Wang, Xuefeng, Gao, Yuwei, He, Hongbin. 2023. CD97 negatively regulates the innate immune response against RNA viruses by promoting RNF125-mediated RIG-I degradation. In Cellular & molecular immunology, 20, 1457-1471. doi:10.1038/s41423-023-01103-z. https://pubmed.ncbi.nlm.nih.gov/37978243/
5. Feng, Xueyi, Song, Dongqiang, Liu, Xiaolan, Wu, Shenwei, Liu, Fubao. 2024. RNF125‑mediated ubiquitination of MCM6 regulates the proliferation of human liver hepatocellular carcinoma cells. In Oncology letters, 27, 105. doi:10.3892/ol.2024.14238. https://pubmed.ncbi.nlm.nih.gov/38298426/
6. Wei, Meng, Mo, Yunhai, Liu, Jialong, Min, Min, Wu, Feixiang. 2022. Ubiquitin ligase RNF125 targets PD-L1 for ubiquitination and degradation. In Frontiers in oncology, 12, 835603. doi:10.3389/fonc.2022.835603. https://pubmed.ncbi.nlm.nih.gov/35965501/
7. Hu, Jiapeng, Ding, Ruiwei, Liu, Shaozhuang, Li, Jianjun, Shang, Yunxiao. 2023. Hypermethylation of RNF125 promotes autophagy-induced oxidative stress in asthma by increasing HMGB1 stability. In iScience, 26, 107503. doi:10.1016/j.isci.2023.107503. https://pubmed.ncbi.nlm.nih.gov/37599832/
8. Yang, Liuzhong, Zhou, Bing, Li, Xiaorui, Huo, Xiaoqing, Miao, Zhanhui. 2015. RNF125 is a ubiquitin-protein ligase that promotes p53 degradation. In Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology, 35, 237-45. doi:10.1159/000369691. https://pubmed.ncbi.nlm.nih.gov/25591766/
9. Jiang, Cuihong, He, Lili, Xiao, Shuai, Zhao, Qi, Liu, Feng. 2022. E3 Ubiquitin Ligase RNF125 Suppresses Immune Escape in Head and Neck Squamous Cell Carcinoma by Regulating PD-L1 Expression. In Molecular biotechnology, 65, 891-903. doi:10.1007/s12033-022-00587-w. https://pubmed.ncbi.nlm.nih.gov/36344734/
Quality Control Standard
Sperm Test
Pre-cryopreservation: Measurement of sperm concentration, determination of sperm viability.
Post-cryopreservation: A vial of cryopreserved sperms is selected for in-vitro fertilization from each batch.
Environmental Standards:SPF
Available Region:Global
Source:Cyagen