Affinage

BECN1

Beclin-1 · UniProt Q14457

Length
450 aa
Mass
51.9 kDa
Annotated
2026-04-28
100 papers in source corpus 46 papers cited in narrative 45 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

BECN1 (Beclin 1) is a central scaffold protein of the class III PI3-kinase (PI3KC3/VPS34) complex that orchestrates autophagosome formation, endosomal trafficking, and regulated cell death. Its coiled-coil domain mediates homodimerization and heterodimerization with ATG14 or UVRAG to assemble distinct PI3KC3 subcomplexes, while its BARA domain undergoes partial β-sheet unfolding to anchor the complex on membranes; these activities are positively regulated by ULK1 phosphorylation at Ser30, AMPK phosphorylation at Thr388, JAK2 phosphorylation at Y333, SUMO3 conjugation at K380, and TRAF6-mediated K63-linked ubiquitination, and negatively regulated by BCL2/BCL2L1 binding to its BH3 domain, Rubicon/GLIPR2 binding to the BARA domain, CAMK2 phosphorylation at Ser295, CUL3–KLHL38- and RNF216-mediated K48-linked ubiquitination and degradation, and ISGylation at multiple lysines (PMID:17893711, PMID:27304906, PMID:29313410, PMID:34131122, PMID:30581147, PMID:31373534, PMID:33977871, PMID:27245989, PMID:33222586, PMID:25906440). Beyond autophagy, AMPK-phosphorylated BECN1 directly binds SLC7A11 to block system Xc⁻ cystine transport and promote ferroptosis, and BECN1 facilitates adiponectin secretion through interaction with the exocyst complex and participates in retrograde endosome-to-Golgi trafficking (PMID:30057310, PMID:34038729, PMID:9105038, PMID:21183797). Disruption of the BECN1–BCL2 interaction by the F121A knock-in mutation constitutively activates autophagy in vivo, sequestering amyloid-β oligomers and preventing Alzheimer's disease-like pathology in mice (PMID:28806762).

Mechanistic history

Synthesis pass · year-by-year structured walk · 20 steps
  1. 1997 High

    Establishing that the BECN1 ortholog Vps30 functions in endosomal sorting revealed its primordial role beyond autophagy — it is required for endosome-to-Golgi retrieval of the vacuolar sorting receptor Vps10p.

    Evidence Temperature-sensitive alleles, subcellular fractionation, and genetic epistasis in S. cerevisiae

    PMID:9105038

    Open questions at the time
    • Mammalian trafficking function not yet demonstrated
    • Whether sorting and autophagy functions are separable was unknown
  2. 2007 High

    Consolidation of BECN1 as a core subunit of the VPS34/PI3KC3 lipid-kinase complex resolved how it mechanistically contributes to autophagosome nucleation via PI3P generation.

    Evidence Genetic complementation, fractionation, and functional studies across yeast, worms, flies, and mammals

    PMID:17893711

    Open questions at the time
    • Structural basis of BECN1 within the complex unresolved
    • Which post-translational modifications regulate complex assembly unknown
  3. 2008 Medium

    Discovery that BECN1 is a caspase substrate provided the first evidence for direct crosstalk between apoptotic and autophagic machineries at the level of BECN1 proteolysis.

    Evidence In vitro caspase cleavage assay and pan-caspase inhibitor treatment in human cells

    PMID:18842334

    Open questions at the time
    • Cleavage sites not mapped at residue resolution in this study
    • Physiological relevance of cleavage fragments unclear
  4. 2009 High

    Identification of NF-κB/p65 as a direct transcriptional activator of the BECN1 promoter established a signaling input linking inflammatory pathways to autophagy gene expression.

    Evidence EMSA, ChIP, promoter reporter assays, and siRNA knockdown in multiple human cell lines

    PMID:19289499

    Open questions at the time
    • Other transcription factors regulating BECN1 not systematically catalogued
    • In vivo relevance not tested
  5. 2011 Medium

    Demonstration that C. elegans BEC-1 controls retrograde endosome-to-Golgi transport of Wntless/MIG-14 confirmed that BECN1's trafficking role is conserved beyond yeast.

    Evidence Genetic analysis, RNAi, and fluorescence microscopy of endosomal markers in C. elegans

    PMID:21183797

    Open questions at the time
    • Whether mammalian BECN1 similarly controls Wntless trafficking not shown
    • Dependence on PI3KC3 activity versus other BECN1 interactions not dissected
  6. 2014 Medium

    Mapping of TRAF6-mediated K63-linked ubiquitination and ARRB1 scaffolding as positive regulators of BECN1–PI3KC3 complex formation revealed that ubiquitin signaling and stress-specific adaptors control autophagy initiation at the BECN1 level.

    Evidence Co-IP, ubiquitination assays with linkage specificity, PI3KC3 kinase activity assays, Arrb1 knockout mice

    PMID:24988431 PMID:30231667

    Open questions at the time
    • K63-ubiquitination sites on BECN1 not mapped
    • Relative contributions of ARRB1 and TRAF6 in different tissues unclear
  7. 2015 Medium

    Multiple studies converged to define the BCL2 family (BCL2, BCL2L1, BCL2L10/BCL-B) as direct BH3-domain-dependent inhibitors of BECN1 autophagy function, operating independently of BAX/BAK1 proapoptotic signaling.

    Evidence BH3 mimetic ABT-737 in BAX/BAK1 DKO cells, BCL2L10 co-IP/knockdown epistasis, VDAC2 stabilization of BECN1–BCL2L1 complex

    PMID:22498477 PMID:25715028 PMID:26060891

    Open questions at the time
    • Quantitative affinities of different BCL2 family members for BECN1 BH3 not compared
    • In vivo relevance of BCL-B and VDAC2 regulation not fully characterized
  8. 2015 High

    BECN1 knockout in human cells showed it is dispensable for LC3 lipidation but essential for proper autophagosome morphology and autophagic flux, redefining its role as a quality-control scaffold rather than an absolute upstream requirement for LC3 conjugation.

    Evidence TALEN-mediated BECN1 KO, electron microscopy, PI3KC3 kinase activity assay

    PMID:25955014

    Open questions at the time
    • Whether compensatory PI3K pathways explain residual LC3 lipidation unknown
    • Long-term cellular consequences of BECN1 loss not fully explored
  9. 2016 High

    High-resolution structures of the BECN1 coiled-coil domain (homodimer and ATG14 heterodimer interface) and the flexible helical domain (FHD) defined the structural logic by which BECN1 switches between inactive homodimer and active ATG14-bound heterodimer states during starvation-induced autophagy.

    Evidence X-ray crystallography (1.46 Å CCD; 2.0 Å FHD), SAXS, DEER-EPR, interface mutagenesis, autophagy flux assays

    PMID:26937551 PMID:27383850

    Open questions at the time
    • Full-length BECN1 structure not yet solved
    • How FHD conformational change is triggered in cells unclear
  10. 2016 High

    Identification of multiple kinases (AMPK at Thr388, CAMK2 at Ser295) that phosphorylate BECN1 with opposing effects on PI3KC3 complex assembly versus BCL2 binding established phosphorylation as a bidirectional regulatory switch for autophagy.

    Evidence In vitro kinase assays, phospho-defective/mimic mutants, co-IP for PI3KC3/BCL2 binding, TRPM2-Ca²⁺ pathway epistasis

    PMID:27245989 PMID:27304906

    Open questions at the time
    • Cross-talk between phosphorylation sites not systematically mapped
    • Phosphatases that reverse these modifications largely unknown
  11. 2017 High

    The Becn1-F121A knock-in mouse, which constitutively disrupts BECN1–BCL2 binding and hyperactivates autophagy, demonstrated that modulating BECN1 activity can prevent amyloid-β accumulation and Alzheimer's-like pathology in vivo.

    Evidence Knock-in mouse crossed with AD model, immunoisolation of autophagosomes, behavioral testing

    PMID:28806762

    Open questions at the time
    • Whether this protection extends to tau pathology unknown
    • Mechanism of Aβ capture by autophagosomes not molecularly defined
  12. 2018 High

    AMPK-mediated phosphorylation of BECN1 at Ser90/93/96 was shown to promote direct binding to SLC7A11 and inhibition of system Xc⁻, establishing a non-autophagic ferroptosis-promoting function for BECN1.

    Evidence Phospho-defective mutant (S90,93,96A), reciprocal co-IP, ferroptosis assays, in vivo tumor models

    PMID:30057310

    Open questions at the time
    • Whether BECN1-SLC7A11 interaction occurs at a specific membrane compartment unknown
    • Stoichiometry and structural basis of BECN1-SLC7A11 binding unresolved
  13. 2018 High

    Cryo-EM and hydrogen-deuterium exchange revealed that the BECN1 BARA domain β-sheet 1 undergoes partial unfolding to insert into membranes, providing a structural mechanism for PI3KC3 complex membrane targeting — exploited by Rubicon and HIV-1 Nef as an inhibitory binding site.

    Evidence Cryo-EM, HDX-MS, protein engineering, giant unilamellar vesicle reconstitution, molecular simulations

    PMID:30581147

    Open questions at the time
    • Lipid specificity of BARA membrane insertion not fully defined
    • How partial unfolding is regulated in vivo unclear
  14. 2018 High

    ULK1 phosphorylation of BECN1 at Ser30 was shown to selectively activate the ATG14-containing PI3KC3-C1 complex (not the UVRAG complex), demonstrating subcomplex-specific kinase regulation.

    Evidence In vitro kinase assay, S30A mutant, complex-specific co-IP, phagophore imaging

    PMID:29313410

    Open questions at the time
    • Whether other ULK1 phosphorylation sites exist on BECN1 not excluded
    • How Ser30 phosphorylation structurally favors ATG14 binding unknown
  15. 2019 High

    SUMO3 conjugation of BECN1 at K380 by PIAS3 (reversed by SENP3) was shown to promote interactions with UVRAG, PIK3C3, and ATG14 and enhance PI3KC3 kinase activity, adding SUMOylation to the post-translational code governing BECN1 complex assembly.

    Evidence SUMOylation site mutagenesis, PI3KC3 activity assay, liver-specific Senp3 KO mice

    PMID:31373534

    Open questions at the time
    • Whether SUMOylation and ISGylation compete at overlapping sites not resolved
    • Tissue specificity of PIAS3-BECN1 regulation not explored
  16. 2019 High

    Crystal structures of BCL2/BCL2L1 with Thr108-phosphorylated BECN1 BH3 peptides showed that STK4/MST1-mediated phosphorylation fine-tunes BCL2 family binding affinity, influenced by membrane-like environments.

    Evidence X-ray crystallography, SPR, MST binding assays, molecular dynamics

    PMID:30626284

    Open questions at the time
    • In vivo relevance of T108 phosphorylation for autophagy regulation not demonstrated
    • Whether STK4 and CAMK2 phosphorylation sites act synergistically unknown
  17. 2020 High

    GLIPR2 was identified as a direct inhibitor of PI3KC3-C1 kinase activity through binding to BECN1 residues 267–284, demonstrating that the BARA-adjacent region serves as a regulatory hotspot distinct from the BCL2-binding BH3 domain.

    Evidence In vitro lipid kinase assay with purified PI3KC3-C1, CRISPR KO in cells and mice, WIPI2 recruitment assay

    PMID:33222586

    Open questions at the time
    • GLIPR2 regulation itself not characterized
    • Whether GLIPR2 competes with ASPP2/APP for the same BECN1 region unclear
  18. 2021 High

    Discovery that CUL3–KLHL38 mediates K48-linked ubiquitination and proteasomal degradation of BECN1 established a dedicated E3 ligase–adaptor pair for BECN1 turnover, complementing earlier identification of RNF216.

    Evidence Mass spectrometry, reciprocal co-IP, K48-linkage-specific ubiquitination assay, cycloheximide chase, CRISPR KO

    PMID:33977871

    Open questions at the time
    • Relative contributions of CUL3/KLHL38 vs. RNF216 in different tissues not compared
    • BECN1 ubiquitination sites targeted by CUL3/KLHL38 not mapped
  19. 2021 Medium

    BECN1 was shown to interact with the exocyst complex via its coiled-coil domain to promote adiponectin secretion, establishing a non-degradative, non-cell-autonomous function for BECN1 in metabolic homeostasis.

    Evidence Becn1-F121A knock-in mice, adipose-specific expression, co-IP with exocyst components, adiponectin secretion and systemic AMPK activation assays

    PMID:34038729

    Open questions at the time
    • Which exocyst subunit directly contacts BECN1 not identified
    • Whether PI3KC3 activity is required for this secretion function not tested
  20. 2024 Medium

    The UFMylation–VCP–ATXN3 axis was shown to stabilize BECN1 by promoting its deubiquitination, adding an additional layer of post-translational control over BECN1 protein levels and PI3KC3 complex assembly.

    Evidence UFMylation site mapping on VCP, ATXN3 deubiquitination assay, PI3KC3 co-IP, VCP knockdown/rescue with K109R mutant

    PMID:38762759

    Open questions at the time
    • Whether ATXN3 removes K48- or K63-linked ubiquitin chains from BECN1 not specified
    • In vivo physiological contexts for UFMylation-dependent BECN1 regulation not explored

Open questions

Synthesis pass · forward-looking unresolved questions
  • A full-length structure of BECN1 within the intact PI3KC3 complex, including conformational dynamics of the FHD and BARA membrane-insertion states, has not been determined; the integration of multiple simultaneous post-translational modifications and their combinatorial effects on BECN1 function remain uncharacterized.
  • No full-length BECN1 structure in the context of PI3KC3 complex
  • Combinatorial PTM code (phosphorylation, ubiquitination, SUMOylation, ISGylation, UFMylation) not systematically dissected
  • Structural basis of BECN1–SLC7A11 interaction in ferroptosis unknown

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0060090 molecular adaptor activity 5 GO:0098772 molecular function regulator activity 3 GO:0008289 lipid binding 1
Localization
GO:0005768 endosome 2 GO:0005829 cytosol 2 GO:0005886 plasma membrane 2 GO:0031410 cytoplasmic vesicle 2
Pathway
R-HSA-9612973 Autophagy 9 R-HSA-162582 Signal Transduction 4 R-HSA-392499 Metabolism of proteins 4 R-HSA-168256 Immune System 3 R-HSA-5357801 Programmed Cell Death 3 R-HSA-5653656 Vesicle-mediated transport 3
Partners
ATG14BCL2BCL2L1PIK3C3RUBCNSLC7A11TRAF6UVRAG
Complex memberships
BECN1-BCL2 inhibitory complexPI3KC3-C1 (VPS34-VPS15-BECN1-ATG14)PI3KC3-C2 (VPS34-VPS15-BECN1-UVRAG)

Evidence

Reading pass · 45 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2007 Atg6/Beclin 1 (BECN1) is a core component of a lipid kinase complex (class III PI3-kinase/Vps34 complex) required for autophagosome formation; yeast Vps30/Atg6 is required for both autophagy and vacuolar protein sorting Genetic complementation, fractionation, and physiological studies in yeast and multiple model organisms Cell research High 17893711
1997 Yeast Vps30 (Atg6/BECN1 ortholog) is required for endosome-to-Golgi retrieval of the vacuolar sorting receptor Vps10p; loss of Vps30 causes mislocalization of Vps10p to the vacuole via a Pep12p-dependent endosomal route Temperature-sensitive allele generation, subcellular fractionation, genetic epistasis The Journal of cell biology High 9105038
2009 NF-κB subunit p65/RelA directly binds a conserved κB site in the BECN1 promoter and upregulates BECN1 transcription, coupling NF-κB signaling to increased autophagy Promoter reporter assays, EMSA, ChIP, siRNA knockdown, Western blot Molecular and cellular biology High 19289499
2016 AMPK phosphorylates BECN1 at Thr388, which is required for autophagy induction upon glucose withdrawal; phosphorylation promotes BECN1 interaction with PIK3C3 and ATG14 while reducing BCL2 binding and homodimerization In vitro kinase assay, phosphorylation-defective/mimic mutants, co-immunoprecipitation, autophagy flux assays Autophagy High 27304906
2018 AMPK-mediated phosphorylation of BECN1 at Ser90/93/96 is required for BECN1-SLC7A11 complex formation, inhibition of system Xc- cystine/glutamate antiporter activity, lipid peroxidation, and ferroptosis shRNA knockdown, phosphorylation-defective mutants (S90,93,96A), co-immunoprecipitation, in vitro ferroptosis assays, in vivo mouse tumor models Current biology : CB High 30057310
2021 IL-6 activates JAK2 which directly phosphorylates BECN1 at Y333, and Y333 phosphorylation is required for PI3KC3 complex formation and IL-6-induced autophagy Co-immunoprecipitation, kinase assays, phospho-mutant constructs, autophagy flux assays Nature communications High 34131122
2008 BECN1 (ATG6) is a caspase substrate; caspase-mediated cleavage of BECN1 links apoptotic and autophagic signaling pathways, and overexpression of BECN1 suppresses cell death In vitro caspase cleavage assay, pan-caspase inhibitor (zVAD), siRNA knockdown, ectopic expression Cancer letters Medium 18842334
2021 CUL3 E3 ubiquitin ligase interacts with BECN1 via the substrate adaptor KLHL38 to promote K48-linked ubiquitination and proteasomal degradation of BECN1, thereby suppressing autophagy Co-immunoprecipitation, mass spectrometry, ubiquitination assay, cycloheximide chase, CRISPR/shRNA Autophagy High 33977871
2014 RNF216 E3 ubiquitin ligase interacts with BECN1 and promotes K48-linked ubiquitination of BECN1 via its TRIAD domain, causing BECN1 degradation and autophagy inhibition in macrophages Co-immunoprecipitation, ubiquitination assay, overexpression/knockdown, bacterial infection model Autophagy Medium 25484083
2018 ULK1 phosphorylates BECN1 at Ser30 specifically within the ATG14-containing PI3KC3 complex (but not the UVRAG complex), and this phosphorylation is required for ATG14-PI3KC3 kinase activation, phagophore formation, and autophagy induction under amino acid starvation In vitro kinase assay, phospho-site mutants (S30A), co-immunoprecipitation, autophagy flux assays, LC3/phagophore imaging Autophagy High 29313410
2016 CAMK2, activated by TRPM2-mediated Ca2+ influx under oxidative stress, phosphorylates BECN1 at Ser295, which decreases BECN1-PIK3C3 association while increasing BECN1-BCL2 binding, thereby inhibiting autophagy In vitro kinase assay, co-immunoprecipitation, TRPM2 knockout/knockdown, phospho-mutant constructs Autophagy High 27245989
2015 BECN1 is ISGylated by ISG15 at Lys117, Lys263, Lys265, and Lys266 (in competition with K63-linked ubiquitination) in response to type I interferon, and this ISGylation negatively regulates autophagy and EGFR degradation dependent on class III PI3K activity; SENP3 deSUMOylates BECN1 at K380 ISGylation assay, site-directed mutagenesis, USP18 deISGylation assay, autophagy flux assays Autophagy Medium 25906440
2019 BECN1 is SUMO3-conjugated by PIAS3 at K380 and deSUMOylated by SENP3; SUMOylation of BECN1 promotes its interaction with UVRAG, PIK3C3, and ATG14, activates PIK3C3 activity, and enhances autophagosome formation SUMOylation assay with site-directed mutagenesis, co-immunoprecipitation, PIK3C3 activity assay, liver-specific Senp3 knockout mouse, autophagic flux assays Autophagy High 31373534
2018 The BECN1 BARA domain (specifically β-sheet 1) undergoes partial unfolding/membrane insertion to mediate PI3KC3 complex membrane targeting; this mechanism is exploited by BECN1 peptides to activate both PI3KC3-C1 and -C2, inhibited by Rubicon binding to the BARA β-sheet 1, and blocked by HIV-1 Nef which also targets this region Hydrogen-deuterium exchange, cryo-EM, protein engineering, giant unilamellar vesicle assays, molecular simulations Molecular cell High 30581147
2016 The BECN1 coiled-coil domain (CCD) forms an antiparallel homodimer; BECN1 CCD interface residues also mediate parallel heterodimer formation with ATG14, and mutations at the heterodimer interface abrogate starvation-induced autophagy without affecting basal autophagy X-ray crystallography (1.46 Å), SAXS, circular dichroism, co-immunoprecipitation with interface mutants, autophagy flux assays Biochemistry High 27383850
2016 BECN1 contains a flexible helical domain (FHD) between the BH3 and coiled-coil domains that is partially disordered and undergoes a disorder-to-helix transition; conserved FHD residues are required for starvation-induced autophagy X-ray crystallography (2.0 Å SAD), circular dichroism, DEER-EPR, SAXS, MD simulations, cellular autophagy assays Biochemistry High 26937551
2019 STK4/MST1 phosphorylates BECN1 at Thr108 within the BH3 domain, modestly increasing BECN1 affinity for BCL2 and BCL2L1; X-ray crystal structures of BCL2 and BCL2L1 with T108-modified BECN1 BH3 peptides indicate the interaction with a conserved histidine is influenced by membrane-like environments X-ray crystallography, biophysical binding assays (SPR, MST), molecular dynamics simulations Autophagy High 30626284
2014 ARRB1 (β-arrestin-1) interacts with both BECN1 and PIK3C3 under ischemic stress to form a BECN1 autophagic core complex; loss of ARRB1 impairs BECN1-PIK3C3 interaction, reduces PIK3C3 kinase activity, and suppresses autophagosome formation, leading to neuronal apoptosis/necrosis Co-immunoprecipitation, PIK3C3 kinase activity assay, Arrb1 knockout mouse model, oxygen-glucose deprivation Autophagy High 24988431
2015 BCL2-BECN1 binding is disrupted by BH3 mimetic ABT-737 in a BAX/BAK1-independent mechanism to induce autophagy, demonstrating that BCL2 inhibits autophagy directly through BECN1 binding rather than indirectly via proapoptotic BCL2 family members Genetic BAX/BAK1 double-knockout cell lines, BCL2-BECN1 co-immunoprecipitation, autophagy flux assays Autophagy Medium 25715028
2017 The Becn1 F121A knock-in mutation disrupts BECN1-BCL2 interaction, leading to constitutively hyperactive autophagy in vivo; this hyperactive autophagy sequesters Aβ oligomers inside autophagosomes and prevents Alzheimer's disease progression Knock-in mouse generation, co-immunoprecipitation, immunoisolation of autophagosomes, behavioral/cognitive testing, in vivo autophagy flux PLoS genetics High 28806762
2015 BECN1 knockout using TALEN in human cells reveals that BECN1 is dispensable for LC3 lipidation but essential for functional autophagosome formation; BECN1-null cells form malformed multi-membrane autophagosome-like structures and have impaired PI3KC3 complex activity and autophagic flux TALEN-mediated gene knockout, electron microscopy, LC3 lipidation assay, PI3KC3 kinase activity assay, autophagy flux Autophagy High 25955014
2020 GLIPR2 binds to BECN1 (amino acids 267-284 region) and directly inhibits the in vitro lipid kinase activity of purified PI3KC3-C1 complex; GLIPR2 knockout increases autophagic flux and PI3P generation in cells and tissues CRISPR-Cas9 knockout, in vitro lipid kinase assay with purified complex, co-immunoprecipitation, autophagic flux assays, WIPI2 recruitment Autophagy High 33222586
2011 BEC-1 (C. elegans BECN1 ortholog) mediates retrograde endosome-to-Golgi transport in addition to autophagy; bec-1 mutants show reduced RME-8 on endosomal membranes, accumulation of abnormal endosomes, and mislocalization/degradation of MIG-14/Wntless C. elegans genetics, fluorescence microscopy, RNAi, morphological analysis of endosomes Autophagy Medium 21183797
2013 Drosophila Atg6 (BECN1 ortholog) is required for autophagy, endocytosis, and protein secretion, but not all these functions overlap with other core autophagy genes; Atg6 mutants show enlarged lymph glands and excess blood cells in a manner not suppressed by p62 or NFκB mutations Drosophila null mutant generation, genetic epistasis, endocytosis/secretion assays, hematopoietic analysis Development (Cambridge, England) Medium 23406899
2015 VDAC2 interacts with both BECN1 and BCL2L1 to stabilize the BECN1-BCL2L1 inhibitory complex in ovarian cells, suppressing autophagy; VDAC2 transgenic pigs show inhibited ovarian autophagy while Vdac2 knockout promotes autophagy Co-immunoprecipitation, transgenic pig model, Vdac2 knockout, autophagy flux assays Autophagy Medium 26060891
2018 TRIM59 regulates BECN1 by two mechanisms: (1) negatively modulating NF-κB pathway to suppress BECN1 transcription, and (2) promoting K48-linked ubiquitination and degradation of TRAF6, thereby reducing TRAF6-induced K63-linked ubiquitination of BECN1 and impairing BECN1-PIK3C3 complex formation Reporter assays, co-immunoprecipitation, ubiquitination assays, autophagy flux, overexpression/knockdown Autophagy Medium 30231667
2014 TRAF6 promotes K63-linked ubiquitination of BECN1, which is required for BECN1-PI3KC3 complex formation and autophagy induction in response to TLR4 stimulation Co-immunoprecipitation, ubiquitination assay, knockdown, TLR4 stimulation assays Autophagy Medium 30231667 31620128 32384667
2016 USP19 deubiquitinase affects BECN1 ubiquitination, promoting autophagosome formation and inhibiting DDX58/RIG-I-mediated type I interferon signaling, revealing a BECN1-USP19 axis linking autophagy and antiviral immunity Co-immunoprecipitation, ubiquitination assays, interferon signaling assays, knockdown Autophagy Low 27096686
2016 HCMV proteins TRS1 and IRS1 contain a BECN1-binding domain (BBD) that is essential for autophagy inhibition; deletion of the BBD from TRS1 abolishes its ability to block autophagy, demonstrating direct binding to BECN1 is required Domain mapping, BBD deletion mutant viruses, co-immunoprecipitation, autophagy assays in multiple cell lines Autophagy Medium 26654401
2015 GADD45A directly interacts with BECN1 (via GADD45A residues 71-81) and disrupts the BECN1-PIK3C3 complex, inhibiting autophagosome initiation; BECN1 knockdown abolishes GADD45A-induced autophagy changes Co-immunoprecipitation, GST pull-down assay, domain mapping, autophagy flux assays Autophagy Medium 26636486
2017 Phosphorylated CAV1 (at Tyr14) interacts with the BECN1/VPS34 complex via CAV1's scaffolding domain under oxidative stress, promoting autophagosome formation and mitochondrial localization of BECN1; PTPN1 phosphatase reverses this by dephosphorylating CAV1 Co-immunoprecipitation, phospho-mutant constructs, Cav1 knockout mouse, LC3 foci imaging, subcellular fractionation Cell death & disease Medium 28542134
2016 BECN1 directly interacts with plasma membrane-associated APP via the evolutionarily conserved domain (ECD, residues 267-337), and ECD subregion deletion (285-299) impairs APP-BECN1 interaction and APP endocytosis/lysosomal degradation without affecting BECN1-PIK3C3 interaction or autophagy; AKT-mediated phosphorylation of BECN1 Ser295 negatively regulates APP-BECN1 association Co-immunoprecipitation, domain deletion mutants, surface APP internalization assays, lysosomal degradation assays, APP metabolite secretion Autophagy Medium 27715386
2021 Becn1 promotes adiponectin secretion in adipose tissue by interacting with components of the exocyst complex via its coiled-coil domain; this is a non-degradative, non-cell-autonomous mechanism by which Becn1 improves systemic insulin sensitivity and activates AMPK Becn1F121A knock-in mice, adipose-specific expression, co-immunoprecipitation with exocyst components, adiponectin secretion assays, AMPK activation measurement Cell reports Medium 34038729
2020 PKD2 forms a protein complex with BECN1 via PKD2's CC1 coiled-coil domain, and this complex formation requires Ca2+ channel activity; PKD2 overexpression induces autophagy through increased BECN1 interaction, while a Ca2+-channel-deficient mutant (D509V) shows diminished BECN1 binding and fails to induce autophagy Co-immunoprecipitation, domain deletion mutants, Ca2+ chelation (BAPTA-AM), PKD2 mutant expression, autophagy flux assays Autophagy Medium 32543276
2024 VCP/p97 is UFMylated at K109 by E3 ligase UFL1; this modification promotes BECN1 stabilization through ATXN3-mediated deubiquitination of BECN1, thereby facilitating PI3KC3 complex assembly and autophagy initiation UFMylation site mapping, ATXN3 deubiquitination assay, co-immunoprecipitation of PI3KC3 complex, VCP knockdown/rescue with UFMylation-defective mutant Autophagy Medium 38762759
2019 HSPB6 wild-type protein interacts with BECN1, preventing BECN1 ubiquitination and proteasomal degradation, and competitively suppresses BECN1-BCL2 binding to stimulate autophagy; the DCM-associated mutant HSPB6S10F shows reduced BECN1 interaction, leading to BECN1 ubiquitination, degradation, and autophagy inhibition Co-immunoprecipitation, ubiquitination assay, cycloheximide chase, autophagy flux assays, transgenic mouse hearts Autophagy Medium 29157081
2020 HIV-1 Nef enhances the association between BECN1 and its inhibitor BCL2 in a PRKN-dependent manner to block autophagy initiation, in addition to previously known effects on autophagy maturation Co-immunoprecipitation, PRKN knockout/knockdown, autophagy flux assays, viral replication assays Autophagy Medium 32097085
2022 USP15 deubiquitinase interacts with BECN1 (not TRAF6) and induces deubiquitination of BECN1, thereby attenuating autophagy induction and lung cancer migration downstream of the TLR4-TRAF6-BECN1 axis CRISPR-Cas9 USP15 knockout, co-immunoprecipitation, deubiquitination assay, cancer migration/invasion assays Cell death & disease Medium 35422093
2019 BECN1 interacts with the tight junction protein occludin at the intestinal epithelial membrane; Tat-beclin 1 peptide activates BECN1 and promotes occludin endocytosis and reduction in total occludin levels, increasing TJ permeability in an autophagy-independent manner Co-immunoprecipitation, immunofluorescence colocalization, permeability assays, BECN1 siRNA, mouse colon perfusion American journal of physiology. Cell physiology Medium 30892937
2016 ASPP2 binds directly to BECN1 and inhibits autophagy by (1) repressing p65/RelA-induced BECN1 transcription via an ASPP2-p65-IκBα complex, and (2) competing with PIK3C3/UVRAG for BECN1 binding while promoting Rubicon-BECN1 interaction, thereby destabilizing the pro-autophagic PI3KC3 complex Co-immunoprecipitation, reporter assays, ChIP, overexpression/knockdown, autophagic flux assays Cell death & disease Medium 27929538
2016 SLC9A3R1 binds to BECN1 via its C-terminal domain, blocks ubiquitin-dependent BECN1 degradation, attenuates BECN1-BCL2 interaction, and stimulates autophagy in breast cancer cells Co-immunoprecipitation, domain deletion mutants, ubiquitination assay, autophagy flux assays Autophagy Medium 26218645
2015 ABHD5 directly competes with caspase-3 for binding to the cleavage sites of BECN1, preventing caspase-3-mediated cleavage and inactivation of BECN1, thereby maintaining autophagic flux; ABHD5 deficiency allows caspase-3 to cleave BECN1 and impair autophagy Co-immunoprecipitation, competitive binding assay, caspase cleavage assay, autophagy flux assays, ABHD5 knockdown/overexpression Autophagy Medium 27559856
2022 Sorafenib activates SHP-1 which dephosphorylates STAT3, downregulates MCL1, and releases BECN1 from MCL1 binding; freed BECN1 then binds SLC7A11 (system Xc-) and inhibits cystine uptake, promoting ferroptosis in hepatocellular carcinoma Co-immunoprecipitation, siRNA knockdown, SHP-1/STAT3 pathway inhibition, MCL1 ectopic expression rescue International journal of molecular sciences Medium 36232407
2023 BECN1 directly binds SLC7A11 (system Xc-) and the BECN1-SLC7A11 complex formation (promoted by SIRT3/AMPK-mediated autophagy) inhibits system Xc- activity, inducing ferroptosis Co-immunoprecipitation, siSIRT3/3-MA autophagy inhibition, erastin-induced ferroptosis assays, in vivo tumor model Biochemical pharmacology Medium 37196680
2015 BCL2L10/BCL-B interacts with the BH3 domain of BECN1 and inhibits autophagy; Bcl-B knockdown triggers autophagic cell death dependent on LC3, BECN1, and ATG5 Co-immunoprecipitation, Bcl-B overexpression/knockdown, autophagy assays with multiple stimuli, genetic epistasis with ATG5/BECN1 Autophagy Medium 22498477

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2018 AMPK-Mediated BECN1 Phosphorylation Promotes Ferroptosis by Directly Blocking System Xc- Activity. Current biology : CB 622 30057310
2007 Physiological functions of Atg6/Beclin 1: a unique autophagy-related protein. Cell research 489 17893711
1997 Endosome to Golgi retrieval of the vacuolar protein sorting receptor, Vps10p, requires the function of the VPS29, VPS30, and VPS35 gene products. The Journal of cell biology 353 9105038
2009 p65/RelA modulates BECN1 transcription and autophagy. Molecular and cellular biology 219 19289499
2012 miR-376b controls starvation and mTOR inhibition-related autophagy by targeting ATG4C and BECN1. Autophagy 211 22248718
2021 IL-6 regulates autophagy and chemotherapy resistance by promoting BECN1 phosphorylation. Nature communications 198 34131122
2008 Caspase-mediated cleavage of ATG6/Beclin-1 links apoptosis to autophagy in HeLa cells. Cancer letters 186 18842334
2016 AMPK regulates autophagy by phosphorylating BECN1 at threonine 388. Autophagy 174 27304906
2021 CUL3 (cullin 3)-mediated ubiquitination and degradation of BECN1 (beclin 1) inhibit autophagy and promote tumor progression. Autophagy 169 33977871
2007 Arabidopsis ATG6 is required to limit the pathogen-associated cell death response. Autophagy 169 17932459
2014 Mutational landscape of the essential autophagy gene BECN1 in human cancers. Molecular cancer research : MCR 159 24478461
2007 An Arabidopsis homolog of yeast ATG6/VPS30 is essential for pollen germination. Plant physiology 151 17259285
2018 ULK1 phosphorylates Ser30 of BECN1 in association with ATG14 to stimulate autophagy induction. Autophagy 138 29313410
2014 Autophagy regulator BECN1 suppresses mammary tumorigenesis driven by WNT1 activation and following parity. Autophagy 136 25483966
2022 HucMSC-derived exosomes delivered BECN1 induces ferroptosis of hepatic stellate cells via regulating the xCT/GPX4 axis. Cell death & disease 130 35395830
2017 A Becn1 mutation mediates hyperactive autophagic sequestration of amyloid oligomers and improved cognition in Alzheimer's disease. PLoS genetics 128 28806762
2014 ARRB1/β-arrestin-1 mediates neuroprotection through coordination of BECN1-dependent autophagy in cerebral ischemia. Autophagy 118 24988431
2011 The Atg6/Vps30/Beclin 1 ortholog BEC-1 mediates endocytic retrograde transport in addition to autophagy in C. elegans. Autophagy 103 21183797
2014 Regulation of autophagy by E3 ubiquitin ligase RNF216 through BECN1 ubiquitination. Autophagy 100 25484083
2017 Cisplatin induces protective autophagy through activation of BECN1 in human bladder cancer cells. Drug design, development and therapy 97 28553083
2018 TRIM59 regulates autophagy through modulating both the transcription and the ubiquitination of BECN1. Autophagy 91 30231667
2016 Mechanistic study of TRPM2-Ca(2+)-CAMK2-BECN1 signaling in oxidative stress-induced autophagy inhibition. Autophagy 89 27245989
2017 Plant Bax Inhibitor-1 interacts with ATG6 to regulate autophagy and programmed cell death. Autophagy 88 28537463
2013 Atg6 is required for multiple vesicle trafficking pathways and hematopoiesis in Drosophila. Development (Cambridge, England) 88 23406899
2014 Pathogenic role of BECN1/Beclin 1 in the development of amyotrophic lateral sclerosis. Autophagy 87 24905722
2016 Analysis of the role of autophagy inhibition by two complementary human cytomegalovirus BECN1/Beclin 1-binding proteins. Autophagy 86 26654401
2015 BAX and BAK1 are dispensable for ABT-737-induced dissociation of the BCL2-BECN1 complex and autophagy. Autophagy 84 25715028
2015 Modification of BECN1 by ISG15 plays a crucial role in autophagy regulation by type I IFN/interferon. Autophagy 82 25906440
2016 Conformational flexibility of BECN1: Essential to its key role in autophagy and beyond. Protein science : a publication of the Protein Society 78 27414988
2015 MYBL2 guides autophagy suppressor VDAC2 in the developing ovary to inhibit autophagy through a complex of VDAC2-BECN1-BCL2L1 in mammals. Autophagy 78 26060891
2008 Autophagy protein 6 (ATG6) is required for pollen germination in Arabidopsis thaliana. Autophagy 78 18227644
2015 Divergent roles of BECN1 in LC3 lipidation and autophagosomal function. Autophagy 74 25955014
2018 Bidirectional Control of Autophagy by BECN1 BARA Domain Dynamics. Molecular cell 72 30581147
2015 A pivotal role of FOS-mediated BECN1/Beclin 1 upregulation in dopamine D2 and D3 receptor agonist-induced autophagy activation. Autophagy 72 26649942
2022 USP15 negatively regulates lung cancer progression through the TRAF6-BECN1 signaling axis for autophagy induction. Cell death & disease 67 35422093
2011 Heat shock protein 90-mediated inactivation of nuclear factor-κB switches autophagy to apoptosis through becn1 transcriptional inhibition in selenite-induced NB4 cells. Molecular biology of the cell 66 21346199
2019 A fine-tuning mechanism underlying self-control for autophagy: deSUMOylation of BECN1 by SENP3. Autophagy 62 31373534
2017 Phosphorylated CAV1 activates autophagy through an interaction with BECN1 under oxidative stress. Cell death & disease 59 28542134
2010 Co-inhibition of BCL-W and BCL2 restores antiestrogen sensitivity through BECN1 and promotes an autophagy-associated necrosis. PloS one 59 20062536
2016 ABHD5 interacts with BECN1 to regulate autophagy and tumorigenesis of colon cancer independent of PNPLA2. Autophagy 58 27559856
2014 Gene of the month: BECN1. Journal of clinical pathology 55 24811486
2014 Berberine attenuates autophagy in adipocytes by targeting BECN1. Autophagy 55 25126729
2020 The autophagy-independent role of BECN1 in colorectal cancer metastasis through regulating STAT3 signaling pathway activation. Cell death & disease 54 32358527
2017 Mir30c Is Involved in Diabetic Cardiomyopathy through Regulation of Cardiac Autophagy via BECN1. Molecular therapy. Nucleic acids 53 28624189
2015 Endothelial Cell Autophagy in Atherosclerosis is Regulated by miR-30-Mediated Translational Control of ATG6. Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology 51 26488467
2022 SHP-1/STAT3-Signaling-Axis-Regulated Coupling between BECN1 and SLC7A11 Contributes to Sorafenib-Induced Ferroptosis in Hepatocellular Carcinoma. International journal of molecular sciences 49 36232407
2022 LncRNA FIRRE functions as a tumor promoter by interaction with PTBP1 to stabilize BECN1 mRNA and facilitate autophagy. Cell death & disease 48 35110535
2019 Intestinal epithelial tight junction barrier regulation by autophagy-related protein ATG6/beclin 1. American journal of physiology. Cell physiology 48 30892937
2020 HIV-1 Nef counteracts autophagy restriction by enhancing the association between BECN1 and its inhibitor BCL2 in a PRKN-dependent manner. Autophagy 47 32097085
2016 From the Cover: Autophagy Induction Contributes to Cadmium Toxicity in Mesenchymal Stem Cells via AMPK/FOXO3a/BECN1 Signaling. Toxicological sciences : an official journal of the Society of Toxicology 44 27492225
2016 BECN1/Beclin 1 sorts cell-surface APP/amyloid β precursor protein for lysosomal degradation. Autophagy 44 27715386
2015 Wheat homologs of yeast ATG6 function in autophagy and are implicated in powdery mildew immunity. BMC plant biology 44 25888209
2012 The anti-apoptotic Bcl-B protein inhibits BECN1-dependent autophagic cell death. Autophagy 44 22498477
2013 Bufalin induces G2/M phase arrest and triggers autophagy via the TNF, JNK, BECN-1 and ATG8 pathway in human hepatoma cells. International journal of oncology 43 23677253
2019 Structural insights into BCL2 pro-survival protein interactions with the key autophagy regulator BECN1 following phosphorylation by STK4/MST1. Autophagy 42 30626284
2014 Atg6/UVRAG/Vps34-containing lipid kinase complex is required for receptor downregulation through endolysosomal degradation and epithelial polarity during Drosophila wing development. BioMed research international 41 25006588
2012 The roles of BECN1 and autophagy in cancer are context dependent. Autophagy 39 22960473
2016 RNF216 contributes to proliferation and migration of colorectal cancer via suppressing BECN1-dependent autophagy. Oncotarget 38 27203674
2016 Downregulation of ASPP2 improves hepatocellular carcinoma cells survival via promoting BECN1-dependent autophagy initiation. Cell death & disease 38 27929538
2012 Recombinant protein rVP1 upregulates BECN1-independent autophagy, MAPK1/3 phosphorylation and MMP9 activity via WIPI1/WIPI2 to promote macrophage migration. Autophagy 38 23051912
2015 SLC9A3R1 stimulates autophagy via BECN1 stabilization in breast cancer cells. Autophagy 37 26218645
2014 ERBB2 overexpression suppresses stress-induced autophagy and renders ERBB2-induced mammary tumorigenesis independent of monoallelic Becn1 loss. Autophagy 36 24492513
2020 GLIPR2 is a negative regulator of autophagy and the BECN1-ATG14-containing phosphatidylinositol 3-kinase complex. Autophagy 35 33222586
2018 Regulation of BECN1-mediated autophagy by HSPB6: Insights from a human HSPB6S10F mutant. Autophagy 35 29157081
2020 PKD2/polycystin-2 induces autophagy by forming a complex with BECN1. Autophagy 34 32543276
2017 A barley homolog of yeast ATG6 is involved in multiple abiotic stress responses and stress resistance regulation. Plant physiology and biochemistry : PPB 34 28343064
2016 The BECN1-USP19 axis plays a role in the crosstalk between autophagy and antiviral immune responses. Autophagy 34 27096686
2007 Somatic mutations of BECN1, an autophagy-related gene, in human cancers. APMIS : acta pathologica, microbiologica, et immunologica Scandinavica 34 17550384
2021 MiR-140-3p Impedes Gastric Cancer Progression and Metastasis by Regulating BCL2/BECN1-Mediated Autophagy. OncoTargets and therapy 32 33953572
2019 Autophagy inhibition via Becn1 downregulation improves the mesenchymal stem cells antifibrotic potential in experimental liver fibrosis. Journal of cellular physiology 31 31508820
2017 MiR-30a inhibits BECN1-mediated autophagy in diabetic cataract. Oncotarget 31 29100392
2021 The autophagy protein Becn1 improves insulin sensitivity by promoting adiponectin secretion via exocyst binding. Cell reports 30 34038729
2020 p62 is Negatively Implicated in the TRAF6-BECN1 Signaling Axis for Autophagy Activation and Cancer Progression by Toll-Like Receptor 4 (TLR4). Cells 30 32384667
2021 Enhanced autophagy in Becn1 knockin mice counteracts aging-related neural stem cell exhaustion and dysfunction. Autophagy 29 34101533
2018 Deficiency of Atg6 impairs beneficial effect of metformin on intestinal stem cell aging in Drosophila. Biochemical and biophysical research communications 29 29496445
2017 miR-1224-5p Mediates Mitochondrial Damage to Affect Silica-Induced Pulmonary Fibrosis by Targeting BECN1. International journal of molecular sciences 28 29112159
2019 Chlorogenic Acid Alleviates Thiram-Induced Tibial Dyschondroplasia by Modulating Caspases, BECN1 Expression and ECM Degradation. International journal of molecular sciences 27 31261680
2016 Identification of BECN1 and ATG14 Coiled-Coil Interface Residues That Are Important for Starvation-Induced Autophagy. Biochemistry 25 27383850
2015 GADD45A inhibits autophagy by regulating the interaction between BECN1 and PIK3C3. Autophagy 25 26636486
2020 The anti-apoptotic proteins Bcl-2 and Bcl-xL suppress Beclin 1/Atg6-mediated lethal autophagy in polyploid cells. Experimental cell research 24 32473226
2024 VCP/p97 UFMylation stabilizes BECN1 and facilitates the initiation of autophagy. Autophagy 23 38762759
2012 Regulation of ATG6/Beclin-1 homologs by abiotic stresses and hormones in rice (Oryza sativa L.). Genetics and molecular research : GMR 23 22930426
2020 Silencing of ATG6 and ATG8 promotes increased levels of triacylglycerol (TAG) in the fat body during prolonged starvation periods in the Chagas disease vector Rhodnius prolixus. Insect biochemistry and molecular biology 22 33022370
2019 CRBN Is a Negative Regulator of Bactericidal Activity and Autophagy Activation Through Inhibiting the Ubiquitination of ECSIT and BECN1. Frontiers in immunology 22 31620128
2017 FoxO1-AMPK-ULK1 Regulates Ethanol-Induced Autophagy in Muscle by Enhanced ATG14 Association with the BECN1-PIK3C3 Complex. Alcoholism, clinical and experimental research 22 28299793
2015 BECN1, corpus luteum function, and preterm labor. Autophagy 22 25646672
2020 Antiviral activity of ISG15 against classical swine fever virus replication in porcine alveolar macrophages via inhibition of autophagy by ISGylating BECN1. Veterinary research 21 32093773
2020 Oncogenic role of MIR516A in human bladder cancer was mediated by its attenuating PHLPP2 expression and BECN1-dependent autophagy. Autophagy 21 32116109
2020 AMPKα1 Regulates Lung and Breast Cancer Progression by Regulating TLR4-Mediated TRAF6-BECN1 Signaling Axis. Cancers 21 33172060
2019 Oncogene SRSF3 suppresses autophagy via inhibiting BECN1 expression. Biochemical and biophysical research communications 21 30654935
2023 SIRT3-mediated autophagy contributes to ferroptosis-induced anticancer by inducing the formation of BECN1-SLC7A11 complex. Biochemical pharmacology 20 37196680
2017 Catalase ameliorates diabetes-induced cardiac injury through reduced p65/RelA- mediated transcription of BECN1. Journal of cellular and molecular medicine 20 28643395
2023 Ginsenoside Rb1 induces hepatic stellate cell ferroptosis to alleviate liver fibrosis via the BECN1/SLC7A11 axis. Journal of pharmaceutical analysis 19 38784156
2016 Conformational Flexibility Enables the Function of a BECN1 Region Essential for Starvation-Mediated Autophagy. Biochemistry 19 26937551
2020 Rabies virus phosphoprotein P5 binding to BECN1 regulates self-replication by BECN1-mediated autophagy signaling pathway. Cell communication and signaling : CCS 17 32948206
2017 Promoter Variant Alters Expression of the Autophagic BECN1 Gene: Implications for Clinical Manifestations of Machado-Joseph Disease. Cerebellum (London, England) 17 28699106
2015 A novel autophagy-independent, oncosuppressive function of BECN1: Degradation of MCL1. Autophagy 17 25837021
2011 Multi-step process of human breast carcinogenesis: a role for BRCA1, BECN1, CCND1, PTEN and UVRAG. Molecular medicine reports 17 22011761
2024 Overcoming multi-drug resistance in SCLC: a synergistic approach with venetoclax and hydroxychloroquine targeting the lncRNA LYPLAL1-DT/BCL2/BECN1 pathway. Molecular cancer 16 39478582
2019 BCL2L10/BECN1 modulates hepatoma cells autophagy by regulating PI3K/AKT signaling pathway. Aging 16 30696802