AMBRA1
- Known as:
- AMBRA1
- Catalog number:
- 001512A
- Product Quantity:
- 250ul
- Category:
- -
- Supplier:
- ABM
- Gene target:
- AMBRA1
Related genes to: AMBRA1
- Gene:
- AMBRA1 NIH gene
- Name:
- autophagy and beclin 1 regulator 1
- Previous symbol:
- -
- Synonyms:
- FLJ20294, KIAA1736, WDR94, DCAF3
- Chromosome:
- 11p11.2
- Locus Type:
- gene with protein product
- Date approved:
- 2008-02-01
- Date modifiied:
- 2016-04-28
Related products to: AMBRA1
Related articles to: AMBRA1
- Melanoma dissemination depends on tumor cell plasticity, extracellular matrix remodeling, and adaptive signaling pathways that promote survival, migration, invasion, and therapeutic resistance. In this study, we investigated the antitumor effects of the plant-derived Kunitz-type protease inhibitor EcTI using both in vitro B16F10-Nex2 melanoma cells and an in vivo murine melanoma model, focusing on adhesion-dependent signaling, autophagy, mitochondrial dysfunction, and regulated cell death. EcTI was efficiently internalized by melanoma cells and showed partial colocalization with lysosomal and mitochondrial compartments, suggesting intracellular trafficking toward these organelles. Treatment reduced cell adhesion to extracellular matrix proteins, particularly fibronectin and laminin, and inhibited migration, invasion, and angiogenic signaling. These effects were associated with modulation of the adhesion-dependent FAK/Src/ERK signaling axis and decreased MMP-9 activity. EcTI also disrupted autophagy, as indicated by accumulation of acidic vesicular organelles, increased LC3-II levels, and modulation of ULK1, Ambra1, and Beclin-1 signaling. In parallel, EcTI induced mitochondrial dysfunction, characterized by loss of mitochondrial membrane potential, intracellular Ca dysregulation, and increased reactive oxygen species production. These alterations triggered regulated cell death involving apoptotic and necroptosis-like mechanisms. Importantly, EcTI significantly suppressed tumor growth in vivo without detectable systemic toxicity and modulated inflammatory mediators associated with tumor progression. Overall, these findings demonstrate that EcTI exerts broad antitumor activity by modulating multiple signaling pathways associated with melanoma progression and represents a promising therapeutic candidate for melanoma treatment. - Source: PubMed
Publication date: 2026/08/13
Bonturi Camila RamalhoSalu Bruno RamosLie Kathleen Chwen MingBonini MárciaSinigaglia Rita de CassiaAlvarez-Flores Miryam PaolaChudzinski-Tavassi Ana MarisaSelistre-de-Araujo Heloisa SobreiroOliva Maria Luiza Vilela - Oral squamous cell carcinomas (OSCCs) are among the most frequent and lethal cancers worldwide. Advanced stage tumors are still treated with standard chemotherapy; however, most patients develop chemotherapy resistance. To uncover new functional biomarkers of cisplatin response, we performed a synthetic lethality genome-wide CRISPR-Cas9 screen in an OSCC cell line. This led to the discovery of AMBRA1 as a regulator of cisplatin sensitivity. In all tested OSCC cell lines and oral primary culture, knockout cells showed increased sensitivity to cisplatin. Mechanistically, we demonstrated an unknown function of AMBRA1 in OSCCs, where loss of AMBRA1 led to an increase in S phase population, expression of genome instability markers, and DNA damage in basal conditions, predisposing cancer cells to an increased sensitivity to cisplatin and other platinum drugs. In summary, we uncovered AMBRA1 as a potential biomarker of response to platinum-based therapies in OSCCs. - Source: PubMed
Publication date: 2026/07/27
Acero-Riaguas LucíaLópez-García IvánPosse-Alonso IreneYáñez-Bartolomé MarianaSan Lorenzo-Vaquero AlejandroBerca CatalinaPérez-Brotóns CésarCastelo BeatrizSastre-Perona Ana - Mitochondrial quality control is essential for cellular homeostasis, particularly in neurons, where mitochondrial dysfunction is implicated in the pathogenesis of neurodegenerative diseases. Mitophagy, the selective degradation of damaged or superfluous mitochondria, plays a central role in maintaining mitochondrial integrity and metabolic balance. This review provides a comprehensive overview of the best-characterized PINK1-PRKN/parkin-dependent mitophagy pathway and the expanding repertoire of PRKN-independent mechanisms, including additional ubiquitin-dependent, receptor-mediated, and lipid-mediated pathways. We explore how these pathways intersect and compensate for one another, highlighting the complexity and adaptability of mitochondrial quality control networks. Furthermore, we discuss how dysregulated mitophagy contributes to the onset and progression of neurodegenerative diseases. By examining the interplay between mitophagy pathways and their regulation under physiological and pathological conditions, this review underscores the therapeutic potential of targeting mitophagy in neurodegeneration. Future studies should aim to decode the spatiotemporal dynamics of these pathways to uncover novel opportunities for clinical intervention. AD: Alzheimer disease; ALS: amyotrophic lateral sclerosis; AMBRA1: autophagy and beclin 1 regulator 1; AMFR/GP78: autocrine motility factor receptor; AMPK: AMP-activated protein kinase; ARIH1: ariadne RBR E3 ubiquitin protein ligase 1; ATG: autophagy related; Aβ: amyloid beta; BCL2L13: BCL2 like 13; BNIP3: BCL2 interacting protein 3; BNIP3L/NIX: BCL2 interacting protein 3 like; CALCOCO2/NDP52: calcium binding and coiled-coil domain 2; CAMc: core autophagy machinery components; CSNK2/CK2: casein kinase 2; DUB: deubiquitinase; DNM1L/DRP1: dynamin 1 like; FKBP8: FKBP prolyl isomerase 8; FUNDC1: FUN14 domain containing 1; GABARAP: GABA type A receptor-associated protein; GLP-1: glucagon-like peptide 1; HD: Huntington disease; HUWE1: HECT, UBA and WWE domain containing E3 ubiquitin protein ligase 1; IMM: inner mitochondrial membrane; iPSC: induced pluripotent stem cell; LIR: LC3-interacting region; MAP1LC3/LC3: microtubule associated protein 1 light chain 3; MARCHF5: membrane associated ring-CH-type finger 5; MCL1: MCL1 apoptosis regulator, BCL2 family member; MDV: mitochondria-derived vesicle; MFN1: mitofusin 1; MFN2: mitofusin 2; MQC: mitochondrial quality control; mtDNA: mitochondrial DNA; MUL1: mitochondrial E3 ubiquitin protein ligase 1; NBR1: NBR1 autophagy cargo receptor; OMM: outer mitochondrial membrane; OMMAD: outer mitochondrial membrane-associated degradation; OPA1: OPA1 mitochondrial dynamin like GTPase; OPTN: optineurin; OXPHOS: oxidative phosphorylation; PARL: presenilin associated rhomboid like; PD: Parkinson disease; PE: phosphatidylethanolamine; PG: phagophore; PGAM5: PGAM family member 5, mitochondrial serine/threonine protein phosphatase; PINK1: PTEN induced kinase 1; PPARGC1A/PGC-1α: PPARG coactivator 1 alpha; PRKN/parkin: parkin RBR E3 ubiquitin protein ligase; PtdIns3K: phosphatidylinositol 3-kinase; RB1CC1/FIP200: RB1 inducible coiled-coil 1; RHOT1/Miro1: ras homolog family member T1; ROS: reactive oxygen species; SIAH1: siah E3 ubiquitin protein ligase 1; SMURF1: SMAD specific E3 ubiquitin protein ligase 1; SOD1: superoxide dismutase 1; SQSTM1/p62: sequestosome 1; TAX1BP1: Tax1 binding protein 1; TBK1: TANK binding kinase 1; TCA: tricarboxylic acid cycle; TFAM: transcription factor A, mitochondrial; TIMM: translocase of inner mitochondrial membrane; TOMM: translocase of outer mitochondrial membrane; Ub: ubiquitin; ULK1: unc-51 like autophagy activating kinase 1; UPRmt: mitochondrial unfolded protein response; UPS: ubiquitin-proteasome system; USP30: ubiquitin specific peptidase 30; VCP: valosin containing protein; VDAC: voltage dependent anion channel; WIPI: WD repeat domain, phosphoinositide interacting. - Source: PubMed
Publication date: 2026/08/13
Rasmussen Laura KristineGomes Moreira DianaOkarmus JustynaSimonsen AnneMeyer Morten - Although a small subset of colorectal cancer (CRC) patients benefit from immunotherapy, oxaliplatin (OXA)-based chemotherapy remains the first-line treatment. However, the widespread development of OXA resistance poses a major clinical challenge, and the underlying molecular mechanisms remain incompletely understood. In this study, we found that Tex10 deficiency markedly enhances OXA sensitivity in CRC cells by inducing cytostatic autophagy in xenograft and patient-derived organoid models. Tex10 mice exhibit markedly reduced tumor numbers and decreased p62 levels in inflammation-induced CRC. Mechanistically, we determined that Tex10 competitively binds BRD9, thereby disrupting the BRD9-BRG1 interaction within the non-canonical BAF (ncBAF) complex, which suppresses AMBRA1 transcription and ULK1 ubiquitination to inhibit autophagy. Furthermore, in silico screening identified gemcitabine (GEM) as a potent Tex10 inhibitor. GEM directly binds to the N268 residue of Tex10, reducing Tex10 abundance and unleashing autophagy. This, in turn facilitates further lysosomal degradation of Tex10, forming a potent positive-feedback loop to overcome OXA resistance. In addition, Tex10 deletion enhances the antitumor efficacy of immunotherapy by inhibiting lysosomal degradation of PD-L1. Collectively, this study uncovers a previously unrecognized antitumor mechanism of GEM and identifies Tex10 as a promising therapeutic target for overcoming OXA resistance and potentiating immunotherapy in CRC. - Source: PubMed
Publication date: 2026/07/29
Xu PingHuang JieGao XiaojinDeng LinDeng YanhengWang DengluYu ChunleiZhang YunxiangLi JingdongXiang Xiaocong - Goose astrovirus (GoAstV) is a newly identified virus affecting geese, leading to goose gout, which is marked by urate deposits in organs and joints. This research investigates the role of autophagy in renal damage caused by GoAstV in goslings. The findings indicated that GoAstV infection in goslings resulted in characteristic clinical manifestations, with renal tissues displaying tubular swelling, inflammatory infiltration, and autophagosome formation. In vivo experiments demonstrated a significant upregulation of mRNA levels for autophagy-related factors, including , , , , , , and , while and levels were notably decreased. At 3 dpi, the protein expression levels of ATG5, Beclin1, and LC3B II/I increased, while P62 levels decreased, suggesting autophagy activation. In vitro analyses revealed that GoAstV infection led to enhanced autophagy; however, the concurrent upregulation of LC3B II/I and P62 proteins suggested an obstruction in the autophagic flux. Upon the inhibition of autophagy with 3-methyladenine (3-MA, autophagy inhibitor), there was a significant reduction in the expression of autophagy-related factors, accompanied by a marked decrease in viral replication rates. In conclusion, GoAstV infection in gosling kidney cells initially triggers enhanced autophagy and subsequently causes a blockage in the autophagic flux. The virus exploits autophagosomes for replication, ultimately resulting in kidney damage. The application of 3-MA effectively inhibits this autophagic process and diminishes viral replication. - Source: PubMed
Publication date: 2026/07/16
Kuang JunLiu ZhenniHuang HaoyuShi YanWu MeiqinWang ZhixianGao XiaonaGuo XiaoquanLiao XinjunLi Haiqin