Ask about this productRelated genes to: RFFL antibody
- Gene:
- RFFL NIH gene
- Name:
- ring finger and FYVE like domain containing E3 ubiquitin protein ligase
- Previous symbol:
- -
- Synonyms:
- rififylin, fring, RNF189, RNF34L, CARP2, CARP-2
- Chromosome:
- 17q12
- Locus Type:
- gene with protein product
- Date approved:
- 2005-08-16
- Date modifiied:
- 2016-08-08
Related products to: RFFL antibody
Related articles to: RFFL antibody
- Cystic fibrosis (CF) is a monogenic disorder caused by mutations in the CFTR gene, which encodes a cAMP-regulated anion channel at the apical plasma membrane (PM) of epithelial cells. CFTR modulators have recently been approved as effective therapies for folding-defective mutations, including the most common variant, F508del. However, no clinically effective treatments are available for nonsense mutations such as G542X, the second most frequent CF-causing mutation. Translational readthrough-inducing drugs (TRIDs), such as G418, can suppress premature termination codons (PTCs) and partially restore full-length CFTR expression, but their therapeutic efficacy remains limited. Notably, combining TRIDs with CFTR modulators enhances functional rescue, suggesting that the restored full-length CFTR may be targeted by protein quality control (QC) pathways. Here, we investigated the QC mechanisms responsible for degrading TRID-induced full-length CFTR proteins harboring nonsense mutations. We identified the E3 ubiquitin ligases RNF5, RNF185, and RFFL as key regulators of CFTR turnover. Among these, RFFL played a particularly critical role in peripheral QC, targeting TRID-induced full-length CFTR for ubiquitination and degradation. Knockdown (KD) of RFFL markedly reduced CFTR ubiquitination, stabilized mature CFTR at the PM, and significantly enhanced functional rescue when TRIDs were combined with CFTR modulators. Enhanced CFTR channel activity confirmed that the stabilized proteins were functional. These findings indicate that RFFL-mediated degradation restricts the therapeutic benefit of TRID-based approaches. Targeting RFFL therefore represents a promising strategy to boost the efficacy of combination therapies involving TRIDs and CFTR modulators, offering new opportunities for the treatment of CF patients carrying nonsense CFTR mutations. - Source: PubMed
Publication date: 2026/02/21
Tateishi HazukiDoi YukakoKamada YukaOkiyoneda Tsukasa - - Source: PubMed
Publication date: 2026/01/14
Pedemonte Nicoletta - Isocitrate dehydrogenase wild-type (IDH wild-type) gliomas represents the most aggressive subtype of diffuse gliomas, characterized by therapeutic resistance and dismal prognosis. Despite advances in molecular classification, reliable prognostic biomarkers for these tumors remain limited, particularly for recurrent disease. This study aims to identify gene expression signatures associated with survival outcomes in recurrent IDH wild-type gliomas, with the goal of improving patient stratification and potential therapeutic targeting. - Source: PubMed
Publication date: 2025/11/20
Liu YangHuse JasonKannan Kasthuri - Cystic fibrosis (CF) is most commonly caused by the ΔF508 mutation in the CFTR gene, leading to misfolding and degradation of the CFTR protein. Although CFTR modulators such as elexacaftor/tezacaftor/ivacaftor (ETI) provide clinical benefit, their efficacy is limited, particularly in patients with rare or poorly responsive CFTR mutations. RFFL, an E3 ubiquitin ligase, plays a central role in peripheral quality control of CFTR, reducing its plasma membrane (PM) expression and attenuating the effects of modulators. Here, we developed antisense oligonucleotides (ASOs) containing artificial nucleic acids to selectively suppress RFFL expression. An optimized -targeting ASO enhanced the efficacy of CFTR modulators by increasing the functional PM expression of ΔF508-CFTR in primary human bronchial epithelial (CF-HBE) cells derived from CF patients. Notably, the ASO also potentiated the effects of ETI on CFTR mutants associated with rare forms of CF, including those with limited responsiveness to modulators. In some cases, the ASO alone restored CFTR levels to those achieved by ETI treatment. These findings establish -targeting ASOs as first-in-class CFTR stabilizers and highlight their potential as a nucleic acid-based therapeutic strategy for CF caused by both common and rare CFTR mutations. - Source: PubMed
Publication date: 2025/10/31
Hinata DaichiKai YukariFukuda RyosukeKamada YukaKasahara YuuyaSasaki KiyomiYoshida TokuyukiObika SatoshiInoue TakaoOkiyoneda Tsukasa - Chronic exposure to environmental pathogens and pollutants can impair CFTR chloride channel function, contributing to chronic obstructive pulmonary disease (COPD). Our previous study demonstrated that pyocyanin (PYO), a COPD-associated pathogen factor, significantly reduces the functional expression of R75Q- or M470V-CFTR, two CFTR polymorphisms found in COPD patients, leading to increased IL-8 production in airway epithelial cells (AEC). In this study, we report that inhibition of RFFL, a ubiquitin ligase that targets CFTR mutants for removal from the plasma membrane (PM), mitigates excessive IL-8 production in AECs expressing R75Q- or M470V-CFTR, even in the presence of PYO. RFFL knockdown (KD) enhanced the functional PM expression of R75Q- or M470V-CFTR under PYO exposure, although it did not prevent PYO-induced CFTR downregulation. Our results indicate that RFFL likely regulates constitutive IL-8 production independently of CFTR, while also modulating pathogen-induced IL-8 expression through a CFTR-dependent mechanism. This highlights the potential of RFFL inhibitors to enhance CFTR function and reduce IL-8 secretion, even amid chronic exposure to environmental pathogens and pollutants, underscoring RFFL inhibition as a promising therapeutic approach for COPD management. - Source: PubMed
Publication date: 2025/06/24
Hinata DaichiBeppu ShioriKamada YukaOkiyoneda Tsukasa