Ask about this productRelated genes to: GBF1 (T1337) antibody
- Gene:
- GBF1 NIH gene
- Name:
- golgi brefeldin A resistant guanine nucleotide exchange factor 1
- Previous symbol:
- -
- Synonyms:
- KIAA0248, ARF1GEF
- Chromosome:
- 10q24.32
- Locus Type:
- gene with protein product
- Date approved:
- 1999-01-14
- Date modifiied:
- 2016-10-05
Related products to: GBF1 (T1337) antibody
Related articles to: GBF1 (T1337) antibody
- Despite the identification of familial Alzheimer's disease (FAD) genes and neuropathological alterations, AD displays complex genetic heterogeneity and molecular pathogenesis that warrant further investigation. GBF1 (Golgi brefeldin A resistant guanine nucleotide exchange factor 1) regulates protein trafficking, and genetic variants of GBF1 are associated with axonal neuropathy, intelligence, and cognitive function. - Source: PubMed
Miller Sean JProkopenko DmitryBai PingMondal PrasenjitScott AbigaelZhang WeiGomm AshleyZhang SiyiChild Daniel DShen NolanWard JosephSchulte ScottLei DanHafler Brian PWang ChangningTanzi Rudolph EZhang Can - Influenza viruses and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are respiratory pathogens that continue to challenge global health due to their efficient transmission and ability to circumvent virus-specific treatments. Targeting host factors that are essential for viral replication may enable the development of broad-spectrum antivirals with reduced resistance potential. Here, we used small interfering RNA (siRNA) to screen 91 host factors previously implicated in influenza virus replication and identified seven that were also required for SARS-CoV-2 replication. Of these, Golgi-specific brefeldin A-resistance factor 1 (GBF1), a guanine nucleotide exchange factor involved in coat protein complex I (COPI) vesicle trafficking, was also involved in human coronavirus 229E replication. We found that GBF1 relocated to sites of viral replication in SARS-CoV-2-infected cells. Using a computational design pipeline, we generated antisense oligonucleotides (ASOs) targeting GBF1. The lead candidate, GBF1-ASO#1502, potently inhibited influenza viruses and SARS-CoV-2 , with nanomolar half-maximal inhibitory concentration (IC) values and favorable selectivity indices. GBF1-targeting ASOs thus represent a promising host-directed antiviral approach for controlling respiratory RNA viruses. - Source: PubMed
Publication date: 2026/01/29
Simanihuruk VictoriaKida YurieTakada KosukeYamaguma HarumiKameoka NatsumiAnzai ItsukiShichinohe ShintaroObika SatoshiKasahara YuuyaWatanabe Tokiko - Triple-negative breast cancer (TNBC) is an aggressive subtype characterized by a lack of targetable receptors, leading to limited treatment options and a critical need for novel therapeutic strategies. This study aimed to evaluate the potential of azelastine, a clinically approved H1-antihistamine, for drug repositioning against TNBC and to elucidate its underlying HRH1-independent mechanism of action. Cell viability assays (CCK-8) were performed on TNBC cell lines (MDA-MB-231 and BT-549) following treatment with azelastine and its major metabolite, desmethyl azelastine. After observing ambiguous clinical associations between HRH1 expression and patient prognosis, HRH1 dependency was assessed through histamine stimulation and HRH1 knockdown (siRNA). Subsequently, the role of ADP-ribosylation factor 1 (ARF1), found to be overexpressed in TNBC and linked to poor prognosis, was investigated using ARF1 knockdown (siRNA), co-treatment with the Golgi-specific brefeldin A-resistance guanine nucleotide exchange factor 1 (GBF1) inhibitor golgicide A (GCA), and co-treatment with the Drp1 inhibitor M-divi 1. Azelastine and desmethyl azelastine potently reduced MDA-MB-231 cell viability in a dose- and time-dependent manner, achieving cell survivals of 61.3 ± 6.1% (30 µM) and 34.9 ± 3.7% (50 µM) for azelastine, and 52.4 ± 12.5% (30 µM) for desmethyl azelastine, respectively, after 72 h, with an IC of 35.93 µM determined for azelastine in MDA-MB-231 cells. Additionally, azelastine significantly reduced the viability of BT-549 cells. Bioinformatic analysis of clinical datasets revealed HRH1 downregulation in tumors and, functionally, neither histamine stimulation nor HRH1 knockdown mediated azelastine cytotoxicity in cell culture. Importantly, ARF1 expression was significantly upregulated in TNBC and associated with poor prognosis. Co-treatment with GCA, preventing ARF1 activation, restored viability to near-control levels, supporting dependence on the GBF1-ARF1 activation axis of azelastine, whereas the Dynamic-related protein 1 (Drp1) inhibitor M-divi 1 not only partially rescued CCK-8-based cell viability but also normalized azelastine-induced loss of MitoTracker™ Red CMXRos signal and partially preserved (4',6-diamidino-2-phenylindole) DAPI-based cell density, indicating Drp1-dependent mitochondrial dysfunction. Furthermore, azelastine selectively reduced p-ERK phosphorylation in the cell signaling pathway. Azelastine exerts potent anticancer effects in TNBC cells via an HRH1-independent, ARF1-dependent mechanism that attenuates the Extracellular signal-regulated kinase (ERK)-Drp1 axis, and induces Drp1-dependent mitochondrial dysfunction, independent of its canonical HRH1 receptor function. This ARF1-dependent mechanism provides strong scientific rationale for the drug repositioning of azelastine as an effective therapeutic agent for ARF1-driven TNBC. - Source: PubMed
Publication date: 2025/12/08
Park Seon UkJung Gi UngPaik Eun KyungLee Jeong-YeonCho Dong CharnChung Hee KyoungJo Hang JoonJung Sung Jun - The secretory pathway is a sophisticated endomembrane machinery designed to transport and deliver proteins and lipids to intracellular organelles and the extracellular space. While the molecular components of the secretory pathway are well understood, less is known about their regulation, especially by mechanical cues. Here, it is reported that substrate stiffness stimulates conventional secretion. A molecular pathway is unravelled that links a mechanical cue through proto-oncogene tyrosine-protein kinase Src (Src) and focal adesion kinase (FAK) kinases to promote the trafficking of secretory proteins out of the Golgi apparatus and prevent their post-Golgi lysosomal degradation. Phosphoproteomic analysis revealed the Golgi-specific Brefeldin A resistance factor 1 (GBF1) as a key downstream mechano-responsive regulator, whose phosphorylation state orchestrates post-Golgi cargo sorting, directing proteins either toward secretion or to lysosomes. Finally, AMP-activated protein kinase (AMPK) is identified as a stiffness-dependent upstream regulator of GBF1 phosphorylation. Together, the data reveal a molecular regulatory loop in which matrix stiffness positively regulates cellular secretion via the Src-FAK-AMPK-GBF1 axis, which can have relevant medical implications in conditions like cancer and fibrosis and their treatment. - Source: PubMed
Publication date: 2025/10/14
Serafino GretaForciniti StefaniaScarpa EdoardoRanieri AntonioSantorelli LuciaDe Blasi GabriellaCostantini SaraLee Eunjoo JunGaleone AntonioCalcagnì AlessiaPirozzi MarinellaDel Mercato Loretta LVenditti RossellaD'Angelo GiovanniParashuraman SeetharamanVerri TizianoGigli GiuseppeSztul Elizabeth SGrumati PaoloRizzello LorisRusso DomenicoRizzo Riccardo - Catharanthus roseus contains nearly 200 bioactive monoterpenoid indole alkaloids (MIAs) that are effective in treating cancer and other diseases. Ethylene plays a significant role in enhancing MIA biosynthesis, and we have found that it greatly induces the accumulation of anhydrovinblastine. However, the regulatory mechanisms underlying this process are not yet fully understood. In this study, a comprehensive analysis of the metabolome and transcriptome of C. roseus was conducted to identify two EIN3/EIL transcription factors, CrEIN3 and CrEIL1, which act as key components mediating the ethylene signal to upregulate MIA biosynthesis. Both CrEIN3 and CrEIL1 were found to upregulate the expression of MIA biosynthetic genes and the activator gene ORCA3, while repressing the expression of repressor genes GBF1 and ZCT1, resulting in increased vinblastine production in C. roseus. CrEIN3 directly binds to the SGD promoter, while CrEIL1 interacts with JA-induced BIS2 to enhance upregulation of the iridoid pathway, thereby further promoting downstream MIA biosynthesis and strengthening the accumulation of bisindole MIAs. Our findings reveal an ethylene-activated regulatory model consisting of CrEIN3 and CrEIL1 that integrates JA-induced BIS2 to cooperatively regulate MIA production in C. roseus, shedding light on the mechanism of ethylene signal regulating MIA biosynthesis. This research provides a foundation for understanding plant hormone regulation of alkaloid metabolism, which will contribute to future efforts in developing high-yielding MIAs in plant or yeast-based platforms. - Source: PubMed
Publication date: 2025/09/08
Deng BofuMiao QingOu ChaoqinPan YuanbingLiu HangFu XueqingLi LingWang YuliangTang KexuanPan Qifang