Ask about this productRelated genes to: RAB5C Blocking Peptide
- Gene:
- RAB5C NIH gene
- Name:
- RAB5C, member RAS oncogene family
- Previous symbol:
- RABL
- Synonyms:
- RAB5CL
- Chromosome:
- 17q21.2
- Locus Type:
- gene with protein product
- Date approved:
- 1999-10-04
- Date modifiied:
- 2013-02-15
Related products to: RAB5C Blocking Peptide
Related articles to: RAB5C Blocking Peptide
- The prevalence of hyperuricemia (HUA) is increasing annually and now affects ∼14% of the population. Uric acid (UA) is the end product of purine metabolism in humans. Either increased production or reduced excretion of UA can induce HUA. Here, we identified RAS and RAB interactor-like (RINL) as a regulator of renal UA excretion and conducted a screen for compounds capable of lowering serum UA concentrations. We found that the () Pro→Ser (P139S) mutation was pathogenic for HUA in a familial pedigree. As a guanine nucleotide exchange factor, RINL activated RAB5C in renal tubular epithelial cells. Activated RAB5C promoted the endocytosis and lysosomal degradation of the UA transporter ATP-binding cassette subfamily G member 2, thereby inhibiting renal UA excretion and contributing to the development of HUA. The hRINL (P139S) mutation inhibited proteasome-mediated degradation of hRINL in renal tubular epithelial cells, causing its accumulation, and the homologous () Pro→Ser (P140S) mutation up-regulated mRINL in mouse kidneys, indicating a gain-of-function mutation. We screened a library of 1500 natural products for RINL inhibitors and, after experimental validation, found that tetrahydrocurcumin bound to RINL and promoted its degradation, thereby ameliorating HUA induced by potassium oxonate treatment, knockout, or secondary to severe malaria and chronic kidney disease in mice. These findings establish RINL as a repressor of UA excretion in both humans and mice and suggest that targeted degradation of RINL represents a promising strategy for HUA treatment. - Source: PubMed
Publication date: 2026/09/23
Han ChangshunHe ChengyongHu WeipingChen ZhiyuanDing XiaoyanYe LingxiaoZhu SihaoZhong LinZhuang ShuniPeng TianyunLi ZixuanHe PanLin LirongRen YingyiRuan FengkaiWang ZizhenZhang YanZhang FucongGuo YitaoYang ChunyanZhang BaodingWang WeiLi ChangguiWang BoLi JianZhang ChensongDeng XianmingZuo Zhenghong - Rab small GTPases (RABs), a family of key regulators governing intracellular membrane trafficking and endosomal dynamics, are extensively implicated in diverse physiological and pathological processes. RAB5c, a critical isoform of the RAB5 subfamily that controls early endosome maturation and vesicle transport, also exerts indispensable functions during viral infection. Previous mass spectrometry analysis preliminarily identified RAB5c as a potential interacting partner of the ORF1B protein encoded by fowl adenovirus serotype 4 (FAdV-4). In this study, we further verified the interaction between RAB5c and ORF1B using co-immunoprecipitation (Co-IP) assays, and confocal microscopy revealed that these two proteins were co-localized in the cytoplasm of leghorn male hepatoma (LMH) cells. Furthermore, the expression pattern of RAB5c and its regulatory role during FAdV-4 infection was evaluated. Results demonstrated that both mRNA and protein levels of RAB5c were significantly upregulated upon FAdV-4 infection. Notably, RAB5c acted as a negative regulator of FAdV-4 replication in LMH cells. Viral titers and viral protein synthesis were remarkably reduced in RAB5c-overexpressing cells, but significantly increased in RAB5c-knockdown cells compared to the control ones. Collectively, these results identified RAB5c as a crucial factor that antagonized FAdV-4 replication. - Source: PubMed
Publication date: 2026/06/27
Gao HuichaoLiu KeyingMa MenghuiChang QingeZhai SaiminLi JianliWang XinweiYang XiaZhao JunZhang XiaozhanWang Zeng - Osteoarthritis is a degenerative joint disease characterized by synovial inflammation and cartilage destruction. This study aimed to investigate the function of in regulating human fibroblast-like synoviocytes (HFLS) and its subsequent impact on chondrocyte degeneration. Differential expression and pathway analyses were performed according to the Gene Expression Omnibus (GEO) dataset. HFLS were stimulated with IL-1β, and was knocked down via transfection. Inflammatory signaling, cytokine expression, and extracellular vesicles (EVs) secretion were assessed. Isolated EVs were characterized by nanoparticle tracking analysis, transmission electron microscopy, and Western blotting. The functional effects of HFLS-derived EVs on chondrocyte inflammation, extracellular matrix metabolism, apoptosis, and viability were evaluated. Bioinformatics analysis identified as a key gene linked to the endocytosis pathway. In IL-1β-stimulated HFLS, expression was upregulated. knockdown reduced the activation of p38 and NF-κB pathways and suppressed pro-inflammatory factors and matrix degradation mediators. Furthermore, deficiency impaired EV secretion and altered their cargo. Crucially, while EVs from control HFLS promoted chondrocyte catabolism, inflammation, and apoptosis, EVs from -knockdown HFLS mitigated these degenerative phenotypes. Our findings demonstrate that , by modulating the biogenesis and composition of HFLS-derived EVs, plays a critical role in driving chondrocyte degeneration, highlighting its importance as a key molecular regulator in osteoarthritis. - Source: PubMed
Publication date: 2026/04/08
Zhang ZhenxingWu YangchunTang XiongfeiLiu ZhigangYang Xuan'angGe Zhen - Noncanonical conjugation of ATG8 proteins, including LC3, to single membranes implicates the autophagy machinery in cell functions unrelated to metabolic stress. One such pathway is LC3-associated phagocytosis (LAP), which aids in phagosome maturation and subsequent signaling upon cargo uptake mediated by certain innate immunity-associated receptors. Here, we show that a specific isoform of RAB5 GTPases, the molecular switches controlling early endosome traffic, is necessary for LAP. We demonstrate that RAB5c regulates phagosome recruitment and function of complexes required for phosphatidylinositol 3-phosphate [PI(3)P] and reactive oxygen species (ROS) generation by macrophages. RAB5c facilitates phagosome translocation of the V-ATPase transmembrane core, which is needed for ATG16L1 binding and consequent LC3 conjugation. RAB5c depletion impaired macrophage elimination of the fungal pathogen and disruption of the V-ATPase-ATG16L1 axis increased susceptibility in vivo. Thus, early endosome-to-phagosome trafficking can be selectively engaged to promote pathogen elimination by directing phagosomal maturation toward LAP. - Source: PubMed
Publication date: 2026/05/08
Freitas-Filho Edismauro GarciaZaidan IsabellaAlzamora-Terrel Daniel LeonardoBifano CarolinaFortes-Rocha Marlonde Castro Patrícia AlvesEugênio Araujo Piraine RenanPinzan Camila Figueiredode Rezende Caroline PatiniBoada-Romero EmilioWileman ThomasAlmeida FaustoGoldman Gustavo HenriqueFlorey OliverCunha Larissa Dias - Glioblastoma (GBM) cells eliminate temozolomide (TMZ) through extracellular vesicles (EVs), a resistance mechanism independent of DNA damage repair that markedly reduces intracellular drug concentration. However, strategies to block this efflux pathway remain poorly explored. Levetiracetam (LEV), a first-line antiepileptic for GBM patients, suppresses seizures by inhibiting synaptic vesicle release, but its potential role in chemotherapeutic efflux has not been investigated. Chemical proteomics identified RAB5A and CD63 as novel LEV-binding targets, and analyses of TCGA datasets further supported their clinical relevance. Mechanistic studies combining co-immunoprecipitation, immunofluorescence, and in silico modeling revealed LEV-mediated disruption of endosomal trafficking and membrane fusion, thereby inhibiting TMZ efflux. Nanoparticle tracking analysis and electron microscopy were used to evaluate EV release, while LC-MS/MS was employed to quantify TMZ at the subcellular and intratumoral levels. Orthotopic GBM models were used to evaluate therapeutic efficacy. RAB5A and CD63 were identified as dual mediators of LEV activity. LEV competitively bound RAB5A, impairing endosomal maturation and TMZ trafficking. LEV also disrupted CD63-RAB35 interaction, promoting RAB35 proteasomal degradation and suppressing plasma membrane fusion. Collectively, LEV reduced TMZ efflux and synergistically enhanced TMZ cytotoxicity in vitro, while in orthotopic models the combination therapy inhibited tumor growth, was accompanied by immune microenvironment remodeling, and prolonged survival. - Source: PubMed
Publication date: 2026/05/06
Zhao JixingLi MingkunZhang QinranLi BoyanQi YanhuaGao ZijieWang QingtongZhao RongrongZhao HongyuZhang KailiangXue HaoLi Gang