Ring Finger Protein 215 Negatively Regulates Type I IFN Production via Blocking NF-κB p65 Activation

Abstract

Germline-encoded pattern recognition receptors (PRRs) recognize molecules frequently found in pathogens (pathogen-associated molecular patterns [PAMPs]) during viral infection. This process induces production of IFNs, leading to expression of IFN-stimulated genes to establish a cellular antiviral state against viral infection. However, aberrant activation of the IFN system may cause immunopathological damage and systemic autoimmune diseases such as systemic lupus erythematosus. Stringent control of IFN signaling activation is critical for maintaining homoeostasis of the immune system; yet, the mechanisms responsible for its precise regulation remain to be elucidated. In this study, we identified that ring finger protein 215 (RNF215), a zinc finger protein, was upregulated by viral infection in human macrophages. In addition, we demonstrated that RNF215 inhibited the production of type I IFNs at least in part via interacting with p65, a subunit of NF-κB, and repressed the accumulation of NF-κB in the promoter region of IFNB1. Moreover, we found that the expression of RNF215 negatively correlated with type I IFNs in patients with systemic lupus erythematosus, indicating that RNF215 plays an important role in the pathogenesis of autoimmune diseases. Collectively, our data identified RNF215 as a key negative regulator of type I IFNs and suggested RNF215 as a potential target for intervention in diseases with aberrant IFN production.

Stromal-epithelial interaction induces GALNT14 in prostate carcinoma cells

“…Although RNF215 showed the highest induction in LNCaP cells, it was not chosen as candidate gene because of the general lack on study data. RNF215 expression is only reported to be upregulated by viral infection in human macrophages and might play an important role in the pathogenesis of autoimmune diseases ( 30 ). In addition, RNF215 is introduced within a four−gene methylation signature to predict the survival outcome of head and neck squamous cell carcinoma ( 31 ).…”

Association of KRAS, NRAS, BRAF and PIK3CA gene mutations with clinicopathological features, prognosis and ring finger protein 215 expression in patients with colorectal cancer

“…At present, to the best of the authors' knowledge, only a few studies of the RNF215 protein have been performed. Wu et al (17) indicated that RNF215 can bind to the NF-kB p65 subunit by partially inhibiting type I interferon (IFN) production and limiting the accumulation of NF-kB in the promoter region of IFNB1. Ma et al (18) suggested that high RNF215 expression was associated with poor overall survival (OS) of head/neck squamous cell carcinoma.…”

Ring finger protein 215 is a potential prognostic biomarker involved in immune infiltration and angiogenesis in colorectal cancer

“…To date, only a few studies have been conducted on the RNF215 protein. Wu et al (8) reported that RNF215 interacts with p65 to reduce the production of type I interferons (IFNs); thus, it is considered to be a key negative regulator of type I IFNs and has been considered a potential target for disease intervention with aberrant IFN production. Ma et al (9) suggested that high RNF215 expression is associated with poor overall survival (OS), demonstrating its function as a head and neck cancer (HNSC) oncogene.…”