Ask about this productRelated genes to: RNF34 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
- Gene:
- RNF34 NIH gene
- Name:
- ring finger protein 34
- Previous symbol:
- -
- Synonyms:
- RIFF, FLJ21786, RIF
- Chromosome:
- 12q24.31
- Locus Type:
- gene with protein product
- Date approved:
- 2001-12-03
- Date modifiied:
- 2016-03-11
Related products to: RNF34 antibody
Related articles to: RNF34 antibody
- The cystic fibrosis transmembrane conductance regulator (CFTR) is a cAMP-regulated anion channel, which is expressed on the apical plasma membrane (PM) of epithelial cells. Mutations in the CFTR gene cause cystic fibrosis (CF), one of the most common genetic diseases among Caucasians. Most CF-associated mutations result in misfolded CFTR proteins that are degraded by the endoplasmic reticulum quality control (ERQC) mechanism. However, the mutant CFTR reaching the PM through therapeutic agents is still ubiquitinated and degraded by the peripheral protein quality control (PeriQC) mechanism, resulting in reduced therapeutic efficacy. Moreover, certain CFTR mutants that can reach the PM under physiological conditions are degraded by PeriQC. Thus, it may be beneficial to counteract the selective ubiquitination in PeriQC to enhance therapeutic outcomes for CF. Recently, the molecular mechanisms of CFTR PeriQC have been revealed, and several ubiquitination mechanisms, including both chaperone-dependent and -independent pathways, have been identified. In this review, we will discuss the latest findings related to CFTR PeriQC and propose potential novel therapeutic strategies for CF. - Source: PubMed
Taniguchi ShogoFukuda RyosukeOkiyoneda Tsukasa - The peripheral protein quality control (periQC) system eliminates the conformationally defective cystic fibrosis transmembrane conductance regulator (CFTR), including ∆F508-CFTR, from the plasma membrane (PM) and limits the efficacy of pharmacological therapy for cystic fibrosis (CF). The ubiquitin (Ub) ligase RFFL is responsible for the chaperone-independent ubiquitination and lysosomal degradation of CFTR in the periQC. Here, we report that the Ub ligase RNF34 participates in the CFTR periQC in parallel to RFFL. An study reveals that RNF34 directly recognizes the CFTR NBD1 and selectively promotes the ubiquitination of unfolded proteins. RNF34 was localized in the cytoplasm and endosomes, where RFFL was equally colocalized. RNF34 ablation increased the PM density as well as the mature form of ∆F508-CFTR rescued at low temperatures. RFFL ablation, with the exception of RNF34 ablation, increased the functional PM expression of ∆F508-CFTR upon a triple combination of CFTR modulators (Trikafta) treatment by inhibiting the K63-linked polyubiquitination. Interestingly, simultaneous ablation of RNF34 and RFFL dramatically increased the functional PM ∆F508-CFTR by inhibiting the ubiquitination in the post-Golgi compartments. The CFTR-NLuc assay demonstrates that simultaneous ablation of RNF34 and RFFL dramatically inhibits the degradation of mature ∆F508-CFTR after Trikafta treatment. Therefore, these results suggest that RNF34 plays a crucial role in the CFTR periQC, especially when there is insufficient RFFL. We propose that simultaneous inhibition of RFFL and RNF34 may improve the efficacy of CFTR modulators. - Source: PubMed
Publication date: 2022/03/09
Taniguchi ShogoIto YukikoKiritani HibikiMaruo AsukaSakai RyoheiOno YujiFukuda RyosukeOkiyoneda Tsukasa - Ubiquitin (Ub) ligation is implicated in active protein metabolism and subcellular trafficking and its impairment is involved in various neurologic diseases. In rat brain, we identified two novel Ub ligases, Momo and Sakura, carrying double zinc finger motif and RING finger domain. Momo expression is enriched in the brain gray matter and testis, and Sakura expression is more widely detected in the brain white matter as well as in many peripheral organs. Both proteins associate with the cell membranes of neuronal and/or glial cells. We examined their Ub ligase activity in vivo and in vitro using viral expression vectors carrying myc-tagged Momo and Sakura. Overexpression of either Momo or Sakura in mixed cortical cultures increased total polyubiquitination levels. In vitro ubiquitination assay revealed that the combination of Momo and UbcH4 and H5c, or of Sakura and UbcH4, H5c and H6 is required for the reaction. Deletion mutagenesis suggested that the E3 Ub ligase activity of Momo and Sakura depended on their C-terminal domains containing RING finger structure, while their N-terminal domains influenced their membrane association. In agreement, Sakura associating with the membrane was specifically palmitoylated. Although the molecular targets of their Ub ligation remain to be identified, these findings imply a novel function of the palmitoylated E3 Ub ligase(s). - Source: PubMed
Araki KazuakiKawamura MeikoSuzuki ToshiakiMatsuda NoriyukiKanbe DaijiIshii KyokoIchikawa TomioKumanishi ToshiroChiba TomokiTanaka KeijiNawa Hiroyuki