Rnf125-flox Mouse

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.