Ask about this productRelated genes to: RNF185 antibody
- Gene:
- RNF185 NIH gene
- Name:
- ring finger protein 185
- Previous symbol:
- -
- Synonyms:
- FLJ38628
- Chromosome:
- 22q12.2
- Locus Type:
- gene with protein product
- Date approved:
- 2005-03-31
- Date modifiied:
- 2019-03-19
Related products to: RNF185 antibody
Related articles to: RNF185 antibody
- The replication protein A (RPA) complex safeguards single-stranded DNA (ssDNA) and coordinates repair during replication stress and homologous recombination (HR), but the mechanisms regulating its timely engagement and release at damage sites are not well defined. Here, we identified RNF185 as a critical E3 ligase that orchestrates temporally distinct patterns of RPA1 ubiquitination-shifting from K6/K63- to K48-linked chains-to precisely regulate HR and replication fork restart upon DNA damage. Mechanistically, RNF185 undergoes ATM/ATR-dependent phosphorylation at threonine 106 and translocates into the nucleus via interaction with NUP88 following DSBs. In the early response phase, RNF185 promotes K6/K63-linked ubiquitination of RPA1, stabilizing RPA1 on ssDNA to facilitate replication fork restart and efficient recruitment of RPA1 to damage sites. At later stages, RNF185 competes with the deubiquitinase OTUB1 for RPA1 binding and facilitates K48-linked ubiquitination at lysine 458, promoting RPA1 degradation and its removal from chromatin. Loss of RNF185 disrupts RPA1 turnover, impairs HR efficiency, destabilizes replication forks, and sensitizes tumor cells to irradiation and cisplatin. In vivo, RNF185 depletion significantly enhances the therapeutic efficacy of radiotherapy. In summary, this study demonstrates that RNF185 is a key regulatory factor in HR and replication fork restart, aiding cells in their response to radio- or chemotherapy induced DNA damage in clinical settings. - Source: PubMed
Publication date: 2026/04/15
Yao ZhichengWang RuruChen BinZhao XipengZhang JieZhou ShenglanXu AnWu LijunZhang JieXu FengZhao Guoping - Polyamine homeostasis is tightly regulated by interconversion and catabolic pathways and has been increasingly implicated in neurodegenerative disorders, including Parkinson's disease (PD), where accumulation of α-synuclein (α-Syn) perturbs neuronal homeostasis. Spermidine/spermine N-acetyltransferase 1 (SAT1) occupies a central position in polyamine interconversion, and alterations in SAT1 activity have been linked to α-Syn toxicity and PD-related neuropathology. To investigate how SAT1 activity influences α-Syn-associated neurodegeneration, we employed a model of neuronal α-Syn expression. SAT1 overexpression reduced α-Syn protein levels, altered its subcellular distribution within the brain, and mitigated α-Syn-induced lifespan shortening. Transcriptomic analyses showed that SAT1 modulates stress-associated gene expression in the α-Syn background, including attenuation of chaperone and ubiquitin-related responses and coordinated changes in pathways linked to mitochondrial function and amino acid metabolism. SAT1 co-expression attenuated α-Syn-associated alterations in genes involved in mitochondrial quality control, including , , , and the mitochondrial ornithine carrier . At the protein level, SAT1 increased mitochondrial-associated signal, enhanced LC3 association with mitochondrial compartments, restored LC3-II/LC3-I ratios in mitochondrial fractions and reduced mitochondrial accumulation of α-Syn. Our findings indicate that SAT1 activity is associated with reduced α-Syn toxicity and altered mitochondrial-associated proteostasis during α-Syn expression. - Source: PubMed
Publication date: 2026/02/16
Bangash Zoya RMatsui HiroyoshiRanxhi BedriTodi Sokol VLeWitt Peter ATsou Wei-Ling - 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 - Nuclear factor erythroid-derived 2 like 1 (NFE2L1) is reported to be embedded in the endoplasmic reticulum (ER) membrane and subsequently undergo N-glycosylation at several asparagine residues as well as other ER-resident factors including cAMP response element binding protein 3 (CREB3)/ATF6 family members. In this study, we investigated the regulation of NFE2L1 protein expression by treating wild-type HEK293 cells and HEK293 cells deficient in selected ER-associated degradation (ERAD) factors with various reagents. NFE2L1 protein expression in wild-type HEK293 cells was negligible, but MG132/bortezomib treatment induced Endo H-resistant two bands. Suppressor/enhancer of lin-12-like (SEL1L)/hydroxymethylglutaryl-CoA (HMG-CoA) reductase degradation 1 (Hrd1) loss increased NFE2L1 protein expression without any stimuli. In these deficient cells, the band shift of NFE2L1 by MG132 was mostly suppressed. Treatment with the valosin containing protein (VCP) inhibitor CB-5083 increased NFE2L1 expression, but deficiencies in other ERAD-associated factors (ER degradation-enhancing α-mannosidase-like protein 2 (EDEM2), thioredoxin domain-containing protein 11 (TXNDC11), gp78, ring finger protein 5 (RNF5), ring finger protein 185 (RNF185), and USP19) did not affect its expression. Comparing the stability of the two intrinsic NFE2L1, which increases with proteasome inhibition, the higher molecular weight form corresponding to full-length form, was more unstable. Therefore, we constructed NFE2L1 genes with mutations in the site where NFE2L1 is cleaved by DDI2 and in the four asparagine residues where N-glycosylation occurs, and found that the high molecular weight form, especially a hypoglycosylated mutant, tended to be more unstable. Taken together, this study using several ERAD disordered models shows that the regulation of NFE2L1 is different in some ways from the regulation of CREB3/ATF6 family, and these findings implicate the diversity of N-glycosylated protein regulation in the ER. - Source: PubMed
Yasui MaikoNagae IzumiMurase RyoichiUchio-Yamada KozueKandeel MahmoudTsujita TadayukiOh-Hashi Kentaro - Genitourinary (GU) malignancies remain a global health challenge. While tissue biopsy is the diagnostic gold standard, its invasive nature and inability to fully capture tumour heterogeneity or minimal residual disease (MRD) highlight the need for non-invasive alternatives. Liquid biopsy, analysing tumour-derived material in plasma or urine, has emerged as a promising tool for diagnosis, surveillance and response monitoring. - Source: PubMed
Harrs Christian FPusala SricharanCheng LiangJazayeri BehzadLi Roger