Affinage

BECN1

Beclin-1 · UniProt Q14457

Length
450 aa
Mass
51.9 kDa
Annotated
2026-06-09
100 papers in source corpus 38 papers cited in narrative 40 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 9/9 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

BECN1/Beclin 1 is the core scaffold of class III PI3-kinase (PIK3C3/VPS34) complexes that nucleate autophagosome formation and govern endosomal membrane trafficking (PMID:16267277, PMID:25955014). It is an intrinsically disordered protein whose N-terminal BH3 subdomain folds into an α-helix only upon binding partners such as BCL2L1, while its C-terminal BARA domain conditionally unfolds its β-sheet-1 to insert into membranes and license PI3KC3 binding and activation (PMID:27046249, PMID:30581147). BECN1 assembles distinct complexes through coiled-coil heterodimerization with ATG14 (autophagy) or association with UVRAG, and its BARA/evolutionarily conserved domain mediates additional cargo interactions (PMID:27383850, PMID:27715386). Complete loss of BECN1 yields malformed multilamellar autophagosome-like structures and abolishes functional PIK3C3 activity without preventing LC3B lipidation, defining it as essential for productive autophagosome morphogenesis (PMID:25955014). Its activity is tuned by an inhibitory interaction with BCL2 that, when disrupted (e.g. F121A), constitutively hyperactivates autophagy in vivo and clears amyloid-β (PMID:28806762, PMID:25715028), and by a dense layer of post-translational modifications: activating phosphorylation by AMPK (Thr388), ULK1 (Ser30 within the ATG14 complex), and JAK2 (Tyr333) all promote PIK3C3 complex formation (PMID:27304906, PMID:29313410, PMID:34131122), whereas CAMK2 (Ser295) phosphorylation inhibits autophagy by displacing PIK3C3 and favoring BCL2 binding (PMID:27245989). Stability and complex assembly are further controlled by PIAS3/SENP3-reversible SUMOylation at K380 and by CUL3-KLHL38-mediated K48 ubiquitination and degradation (PMID:31373534, PMID:33977871). Multiple direct binding partners gate PIK3C3 activity, including the inhibitors GLIPR2 and GADD45A and the positive co-factor ARRB1 (PMID:33222586, PMID:26636486, PMID:24988431). Beyond canonical autophagy, AMPK-dependent phosphorylation at Ser90/93/96 drives a BECN1-SLC7A11 complex that blocks system Xc- and promotes ferroptosis (PMID:30057310); BECN1 acts upstream of PARK2 in mitophagy and relocalizes with PINK1 to mitochondria-associated membranes to seed omegasomes (PMID:24879156, PMID:28368777); it promotes exocyst-dependent adiponectin secretion (PMID:34038729); and nuclear BECN1 scaffolds CHK2-CDC25C to enforce the G2/M checkpoint after irradiation (PMID:32802407). A deeply conserved trafficking role predates these functions, with orthologs required for retrograde endosome-to-Golgi transport and secretion across yeast, worm, and fly (PMID:9105038, PMID:21183797, PMID:23406899).

Mechanistic history

Synthesis pass · year-by-year structured walk · 14 steps
  1. 1997 High

    Established the ancestral function of the BECN1 ortholog before autophagy was attached to it, showing the gene is required for receptor-mediated vacuolar protein sorting.

    Evidence Yeast genetics, subcellular fractionation, and epistasis with sec1/pep12 in VPS30 mutants

    PMID:9105038

    Open questions at the time
    • Did not connect VPS30 to autophagy
    • No molecular partners or biochemical activity defined
  2. 2005 High

    Resolved that the ortholog partitions into two functionally distinct PI3-kinase complexes, foreshadowing the autophagy-versus-sorting division of labor later mapped to ATG14 and UVRAG.

    Evidence Yeast complementation and epistasis distinguishing PI3K complex I (autophagy) from complex II (CPY sorting)

    PMID:16267277

    Open questions at the time
    • Complex-specific subunits in metazoans not yet identified
    • Mechanism of complex switching unknown
  3. 2008 Medium

    Linked BECN1 directly to apoptotic signaling by showing it is a caspase substrate and a death modulator, framing autophagy-apoptosis crosstalk.

    Evidence In vitro caspase cleavage with zVAD block, knockdown/overexpression, TRAIL death assays

    PMID:18842334

    Open questions at the time
    • Cleavage sites not mapped here
    • Single-lab study without in vivo validation
  4. 2009 High

    Identified transcriptional control of BECN1 by NF-κB p65/RelA, explaining how autophagic capacity is set at the gene-expression level.

    Evidence Promoter analysis, EMSA, ChIP, knockdown, and flux assays in T cells

    PMID:19289499

    Open questions at the time
    • Stimulus-specific control of the κB site not fully delineated
  5. 2014 High

    Placed BECN1 upstream of Parkin in mitophagy and identified ARRB1 as a cofactor for PIK3C3 activity, expanding BECN1 beyond bulk autophagy.

    Evidence Reciprocal Co-IP, knockdown/KO mice, PARK2 translocation imaging, and PIK3C3 kinase assays

    PMID:24879156 PMID:24988431

    Open questions at the time
    • How BECN1 enables PARK2 translocation mechanistically unclear
    • Whether ARRB1 acts only under ischemia not resolved
  6. 2016 High

    Defined the structural basis of BECN1 function: intrinsic disorder of the N-terminus, conditional folding of the BH3 helix, ATG14 coiled-coil heterodimerization, and BARA β-sheet-1 membrane insertion driving PIK3C3 activation.

    Evidence NMR, X-ray crystallography, SAXS, cryo-EM, HDX, GUV membrane-insertion assays, and mutagenesis

    PMID:27046249 PMID:27383850 PMID:30581147

    Open questions at the time
    • Full architecture of membrane-engaged complex II not resolved
    • How modifications change the disordered ensemble unknown
  7. 2016 High

    Demonstrated that AMPK and CAMK2 phosphorylation act as opposing switches on the BECN1-BCL2/PIK3C3 equilibrium, coupling metabolic and Ca2+/oxidative stress to autophagy decisions.

    Evidence In vitro kinase assays, phospho-mutants, Co-IP, Ca2+ imaging, and in vivo APAP liver injury model

    PMID:27245989 PMID:27304906

    Open questions at the time
    • Hierarchy among the many phosphosites not integrated
    • Crosstalk between Thr388 and Ser295 not tested together
  8. 2016 Medium

    Revealed an autophagy-independent trafficking role in which the BECN1 ECD binds APP and routes it to lysosomal degradation, reducing amyloidogenic processing.

    Evidence Domain-deletion mutants, Co-IP, surface internalization and lysosomal degradation assays, AKT phosphomimetics

    PMID:27559856 PMID:27715386

    Open questions at the time
    • Single-lab evidence for APP route
    • Relationship to canonical PIK3C3 trafficking unclear
  9. 2018 High

    Separated a ferroptosis-promoting function from autophagy by showing AMPK-driven Ser90/93/96 phosphorylation builds a BECN1-SLC7A11 complex that blocks system Xc-.

    Evidence Phospho-defective mutants, reciprocal Co-IP, lipid peroxidation assays, and in vivo tumor models

    PMID:30057310

    Open questions at the time
    • Whether membrane insertion is required for SLC7A11 inhibition unknown
    • Structural basis of the BECN1-SLC7A11 interface undefined
  10. 2018 High

    Showed ULK1 selectively activates the ATG14-containing complex via Ser30, establishing complex-specific upstream control of PIK3C3 activation.

    Evidence In vitro kinase assays, phospho-specific antibodies, CRISPR knockouts, and phagophore imaging

    PMID:29313410

    Open questions at the time
    • No equivalent activating mark identified for the UVRAG complex
  11. 2019 High

    Defined SUMOylation (PIAS3/K380) reversed by SENP3 as a regulatory layer that enhances BECN1 binding to UVRAG, ATG14, and PIK3C3, and refined the BH3-T108 BCL2 interaction biophysically.

    Evidence SUMO pull-down, Co-IP, liver-specific Senp3 KO mice, K380 mutants, plus crystallography and SPR/MST of T108 BH3 peptides

    PMID:30626284 PMID:31373534 PMID:32802407

    Open questions at the time
    • T108 phosphorylation produces only modest affinity changes
    • Nuclear G2/M scaffolding role (CHK2-CDC25C) shown by single lab
  12. 2020 High

    Identified GLIPR2 as a direct inhibitor of the purified PtdIns3K-C1 lipid kinase, providing reconstituted evidence for negative regulation at the catalytic step.

    Evidence CRISPR KO in cells and mice, in vitro kinase assay with purified complex, WIPI2/PtdIns3P recruitment assays

    PMID:33222586

    Open questions at the time
    • Physiological signals controlling GLIPR2 binding unknown
  13. 2021 High

    Extended BECN1 activation to cytokine signaling (JAK2/Y333) and to non-degradative metabolic secretion via exocyst-dependent adiponectin release.

    Evidence Co-IP, phospho-specific analysis, PIK3C3 complex assays, and adipose-specific Becn1 knock-in mice

    PMID:34038729 PMID:34131122

    Open questions at the time
    • Mechanistic link between Y333 and membrane insertion unmapped
    • Exocyst-binding interface not structurally defined
  14. 2024 Medium

    Connected VCP UFMylation to BECN1 stabilization through ATXN3-mediated deubiquitination, adding a further proteostatic input to PtdIns3K assembly.

    Evidence Co-IP, MS, UFMylation/ubiquitination assays, and VCP K109 mutant rescue of autophagy

    PMID:38762759

    Open questions at the time
    • Single-lab study
    • Which ubiquitin ligase ATXN3 antagonizes on BECN1 not defined

Open questions

Synthesis pass · forward-looking unresolved questions
  • How the dozens of post-translational marks, competing binding partners, and conditional structural states are integrated in space and time to set PIK3C3 output across autophagy, trafficking, ferroptosis, and nuclear checkpoint roles remains unresolved.
  • No unified model coordinating modification hierarchy with complex I/II partitioning
  • Structural basis of autophagy-independent partner switching (SLC7A11, occludin, CHK2/CDC25C, exocyst) undefined
  • In vivo contributions of individual marks to each non-canonical function not dissected

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0060090 molecular adaptor activity 3 GO:0098772 molecular function regulator activity 3 GO:0008289 lipid binding 1
Localization
GO:0005739 mitochondrion 3 GO:0005768 endosome 3 GO:0005829 cytosol 2 GO:0005634 nucleus 1 GO:0005783 endoplasmic reticulum 1
Pathway
R-HSA-5653656 Vesicle-mediated transport 3 R-HSA-8953897 Cellular responses to stimuli 3 R-HSA-9612973 Autophagy 3 R-HSA-5357801 Programmed Cell Death 2 R-HSA-1640170 Cell Cycle 1
Partners
ARRB1ATG14BCL2GLIPR2PARK2PIK3C3SLC7A11UVRAG
Complex memberships
PI3KC3 complex I (BECN1-ATG14-PIK3C3)PI3KC3 complex II (BECN1-UVRAG-PIK3C3)

Evidence

Reading pass · 40 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1997 VPS30 (yeast BECN1 ortholog) is required for retrograde transport of the vacuolar sorting receptor Vps10p from the prevacuolar endosome back to the Golgi; loss-of-function causes Vps10p to mislocalize to the vacuolar membrane and CPY to be missorted and secreted. Yeast genetics, subcellular fractionation, temperature-conditional alleles, epistasis with sec1 and pep12 mutations The Journal of cell biology High 9105038
2005 VPS30/ATG6 in yeast is a component of two distinct PI3-kinase complexes: PI3K complex I (required for autophagy) and complex II (required for the CPY-to-vacuole sorting pathway). Excess soluble A1PiZ uses the CPY pathway, while aggregated A1PiZ uses the autophagy pathway for vacuolar delivery. Yeast complementation, genetic epistasis, characterization of A1PiZ degradation-deficient mutants Molecular biology of the cell High 16267277
2009 The NF-κB family member p65/RelA directly binds a conserved κB site in the BECN1 promoter and transcriptionally upregulates BECN1 mRNA and protein, leading to increased autophagy; this was demonstrated in Jurkat cells upon PMA-ionomycin stimulation and in primary T cells. Promoter analysis, EMSA, ChIP, siRNA knockdown, western blot, autophagy flux assays Molecular and cellular biology High 19289499
2016 AMPK phosphorylates BECN1 at Thr388, which is required for autophagy upon glucose withdrawal. The T388A phosphorylation-defective mutant has higher BCL2 affinity, reduced interaction with PIK3C3 and ATG14, and decreased autophagy; the phosphomimetic T388D shows stronger PIK3C3/ATG14 binding and higher autophagy. In vitro kinase assay, phosphorylation-defective and phosphomimetic mutants, co-immunoprecipitation, autophagy flux assays Autophagy High 27304906
2016 BECN1 BARA domain β-sheet 1 can partially unfold and insert into membranes to enable PI3KC3 complex binding to membranes. Rubicon inhibits and HIV-1 Nef inhibits PI3KC3 complex II via this BARA domain; a BECN1 β-sheet-1 derived peptide activates both PI3KC3 complexes I and II. Cryo-EM, hydrogen-deuterium exchange, protein engineering, giant unilamellar vesicle assays, molecular dynamics simulations Molecular cell High 30581147
2016 The X-ray crystal structure of the antiparallel BECN1 CCD homodimer was determined at 1.46 Å. BECN1 forms a parallel heterodimer with ATG14 via their CCDs; mutations of interface residues impair BECN1:ATG14 heterodimerization, reduce co-immunoprecipitation of the partner, and abrogate starvation-induced but not basal autophagy. X-ray crystallography, circular dichroism, SAXS, co-immunoprecipitation, mutagenesis, autophagy flux assays Biochemistry High 27383850
2018 AMPK-mediated phosphorylation of BECN1 at Ser90/93/96 is required for the formation of a BECN1-SLC7A11 complex that directly blocks system Xc- activity, induces lipid peroxidation, and promotes ferroptosis. A phosphorylation-defective S90,93,96A mutant reverses BECN1-induced ferroptosis, distinct from autophagy-dependent BECN1 function. shRNA knockdown, siRNA, phosphorylation-defective mutants, co-immunoprecipitation, lipid peroxidation assays, in vivo tumor models Current biology : CB High 30057310
2018 ULK1 phosphorylates BECN1 at Ser30 specifically in the ATG14-containing (but not UVRAG-containing) complex, requiring ATG13 and RB1CC1. Ser30 phosphorylation activates the ATG14-containing PIK3C3 complex and stimulates autophagosome formation in response to amino acid starvation, hypoxia, and MTORC1 inhibition; the S30A mutation suppresses all these responses. In vitro kinase assay, phospho-specific antibodies, co-immunoprecipitation, CRISPR knockouts, autophagy flux assays, phagophore imaging Autophagy High 29313410
2019 STK4/MST1 phosphorylates BECN1 at T108 within its BH3 domain, increasing BECN1 affinity (modestly, <2-fold) for anti-apoptotic BCL2 and BCL2L1. Crystal structures of BCL2 and BCL2L1 with T108-modified BECN1 BH3 peptides showed no persistent electrostatic interaction with the conserved histidine; the interaction can be stabilized by local environmental factors such as detergent/membranes. X-ray crystallography, surface plasmon resonance, microscale thermophoresis, molecular dynamics, biophysical binding studies Autophagy High 30626284
2016 BECN1 N-terminal domain (residues 1–150) is intrinsically disordered as determined by NMR spectroscopy. The BH3 subdomain forms an α-helix upon interaction with BCL2L1 but reverts to disordered state upon competitive inhibitor-mediated dissociation. No significant interdomain contacts between N- and C-terminal domains were detected. NMR spectroscopy, biophysical characterization (CD, size-exclusion chromatography), competitive inhibitor dissociation assay Autophagy High 27046249
2014 BECN1 interacts with PARK2 (Parkin) in the cytosol. Loss of BECN1 inhibits CCCP- or PINK1 overexpression-induced PARK2 translocation to mitochondria, prevents MFN2 ubiquitination by PARK2, and rescues MFN2-loss-induced suppression of mitochondrial fusion, placing BECN1 upstream of PARK2 in mitophagy initiation. Co-immunoprecipitation, siRNA knockdown, fluorescence imaging of PARK2 translocation, MFN2 ubiquitination assay, mitochondrial fusion assay Autophagy High 24879156
2017 Following mitophagic stimuli, endogenous PINK1 and BECN1 relocalize to mitochondria-associated membranes (MAM), where they promote enhancement of ER-mitochondria contact sites and formation of omegasomes (autophagosome precursors). PINK1 silencing impairs BECN1 enrichment at MAM independently of PARK2. Subcellular fractionation, immunofluorescence, proximity ligation assay, siRNA knockdown, live imaging of omegasome formation Autophagy High 28368777
2017 Knock-in of F121A mutation in mouse Becn1 reduces interaction of BECN1 with its inhibitor BCL2, leading to constitutively active autophagy. This hyperactivated autophagy sequestrates amyloid-β oligomers inside autophagosomes and prevents cognitive decline in AD mouse models; disrupting BECN1-BCL2 binding is sufficient to hyperactivate autophagy in vivo. Knock-in mouse model, co-immunoprecipitation, autophagy flux assays, immunoisolation of autophagosomes, behavioral testing PLoS genetics High 28806762
2008 ATG6/BECN1 is a caspase substrate; caspases directly cleave BECN1 in a process blocked by pan-caspase inhibitor zVAD. Ectopic BECN1 expression suppresses cell death while BECN1 knockdown sensitizes cells to TRAIL-induced cell death, linking apoptotic and autophagic signaling. In vitro caspase cleavage assay, zVAD inhibition, siRNA knockdown, ectopic expression, cell death assays Cancer letters Medium 18842334
2016 CAMK2, activated by TRPM2-mediated Ca2+ influx under oxidative stress, phosphorylates BECN1 at Ser295. This phosphorylation decreases BECN1-PIK3C3 association and increases BECN1-BCL2 binding, resulting in autophagy inhibition. The TRPM2-Ca2+-CAMK2-BECN1 signaling cascade also operates in APAP-induced liver injury. Co-immunoprecipitation, phospho-specific antibodies, siRNA knockdown, Ca2+ imaging, pharmacological inhibition, in vivo APAP model Autophagy High 27245989
2021 IL-6 activates autophagy via a JAK2-BECN1 pathway: IL-6 triggers JAK2-BECN1 interaction, and JAK2 phosphorylates BECN1 at Y333. Y333 phosphorylation is required for BECN1 activation and IL-6-induced autophagy by regulating PI3KC3 complex formation. Co-immunoprecipitation, phospho-specific antibodies, in vitro kinase assay (implied), siRNA/mutant analysis, PI3KC3 complex assay Nature communications High 34131122
2021 CUL3 (cullin 3) E3 ubiquitin ligase interacts with BECN1 and promotes K48-linked ubiquitination and proteasomal degradation of BECN1, with KLHL38 serving as the substrate adaptor for this CUL3 complex. CUL3-mediated BECN1 degradation decreases autophagic activity. Co-immunoprecipitation, mass spectrometry, ubiquitination assay, cycloheximide chase, KLHL38 adaptor validation Autophagy High 33977871
2019 BECN1 is SUMOylated by PIAS3 predominantly at K380 (SUMO3-conjugated) and deSUMOylated by SENP3. Starvation-induced SUMOylation of BECN1 enhances its interaction with UVRAG, PIK3C3, and ATG14, promoting PIK3C3 activity and autophagosome formation; SENP3-mediated deSUMOylation impairs BECN1-PIK3C3 complex formation and fine-tunes autophagy. SUMO pull-down, co-immunoprecipitation, conditional knockout mice, PI3KC3 activity assay, mutagenesis (K380) Autophagy High 31373534
2015 GADD45A directly interacts with BECN1 (binding mapped to GADD45A residues 71–81) and dissociates the BECN1-PIK3C3 complex, thereby inhibiting autophagosome initiation. BECN1 knockdown abolishes autophagy alterations induced by GADD45A. Co-immunoprecipitation, GST affinity pull-down, domain mapping, western blot, autophagy flux assays Autophagy Medium 26636486
2015 Complete TALEN-mediated knockout of BECN1 in human cells does not abolish LC3B lipidation but leads to malformed autophagosome-like structures with multiple membrane layers and disrupted PIK3C3 complex activity and autophagy flux, demonstrating that BECN1 is essential for functional autophagosome formation but not LC3B lipidation per se. TALEN-mediated knockout, electron microscopy, fluorescence microscopy, autophagy flux assay, PI3KC3 kinase activity assay Autophagy High 25955014
2014 ARRB1 interacts with BECN1 and PIK3C3 under ischemic conditions, and Arrb1 deletion disrupts the BECN1-PIK3C3 interaction and markedly reduces PIK3C3 kinase activity, impairing autophagosome formation and promoting neuronal death during cerebral ischemia. Co-immunoprecipitation, Arrb1 knockout mice, in vivo ischemia model, PIK3C3 kinase activity assay, cell death assays Autophagy High 24988431
2018 TRIM59 regulates BECN1 through two mechanisms: (1) negatively modulating NF-κB pathway to suppress BECN1 transcription, and (2) promoting K48-linked ubiquitination of TRAF6, leading to TRAF6 proteasomal degradation and reduced TRAF6-induced K63-linked ubiquitination of BECN1, thereby impairing BECN1-PIK3C3 complex formation. Co-immunoprecipitation, ubiquitination assays, luciferase reporter (NF-κB), western blot, siRNA knockdown Autophagy Medium 30231667
2017 Phosphorylation of CAV1 at tyrosine-14 is required for interaction of CAV1 (via its scaffolding domain) with the BECN1/VPS34 complex under oxidative stress, facilitating autophagosome formation and localization of BECN1 to mitochondria. PTPN1 phosphatase reduces CAV1 phosphorylation and inhibits this autophagy activation. Co-immunoprecipitation, phospho-specific antibodies, CAV1 knockout cells, Cav1 KO mice, in vivo ischemia model, fluorescence imaging Cell death & disease Medium 28542134
2016 ABHD5 directly competes with CASP3 for binding to BECN1 cleavage sites, preventing BECN1 from being cleaved and inactivated by CASP3, thereby preserving autophagic flux. ABHD5 deficiency allows CASP3 to cleave BECN1, impairing autophagy and augmenting genomic instability. Co-immunoprecipitation, competitive binding assays, caspase cleavage assays, autophagy flux assays Autophagy Medium 27559856
2020 GLIPR2 binds to BECN1 (at residues 267–284) and directly inhibits purified PtdIns3K-C1 lipid kinase activity in vitro. GLIPR2 knockout in cells and mice increases autophagic flux and PtdIns3P generation, confirming GLIPR2 as a negative regulator of PtdIns3K-C1. CRISPR-Cas9 knockout (cells and mice), in vitro PI3K activity assay with purified complex, autophagy flux assays, PtdIns3P WIPI2 recruitment assay Autophagy High 33222586
2018 HSPB6 wild-type interacts with BECN1 to protect it from ubiquitination and proteasomal degradation, and competitively suppresses BECN1-BCL2 binding to stimulate autophagy. The DCM-associated HSPB6S10F mutant has reduced interaction with BECN1, leading to BECN1 ubiquitination, proteasomal degradation, impaired autophagy flux, and increased apoptosis. Co-immunoprecipitation, ubiquitination assay, transgenic mouse model, autophagy flux assay, cardiac functional analysis Autophagy Medium 29157081
2016 BECN1 interacts with plasma membrane-associated APP via its evolutionarily conserved domain (ECD, residues 267–337), and recruits PIK3C3 and UVRAG. BECN1 promotes surface APP internalization, sorting to endolysosomes, lysosomal degradation of APP, and reduction of secreted APP metabolites. AKT-mediated phosphorylation of BECN1 Ser295 inhibits APP-BECN1 interaction and APP degradation. Co-immunoprecipitation, BECN1 domain-deletion mutants, surface APP internalization assay, lysosomal degradation assay, sAPP secretion measurement, AKT inhibitors/phosphomimetics Autophagy Medium 27715386
2021 Becn1 enhances adiponectin secretion by interacting with components of the exocyst complex via its coiled-coil domain. Adipose-specific Becn1F121A (autophagy-hyperactive) expression is sufficient to increase adiponectin secretion, activate systemic AMPK, and improve insulin sensitivity through a non-cell-autonomous, non-degradative mechanism. Adipose-specific knock-in mouse model, co-immunoprecipitation with exocyst components, adiponectin secretion assay, AMPK activation measurement in distal tissues Cell reports High 34038729
2019 Beclin 1 co-immunoprecipitates with the tight junction protein occludin, and BECN1 activation promotes occludin endocytosis and reduces total occludin levels, increasing intestinal TJ permeability in an autophagy-independent manner. Induction of autophagy terminates this constitutive BECN1 function and enhances TJ barrier. Co-immunoprecipitation, BECN1 siRNA knockdown, Tat-beclin 1 peptide, autophagy induction, TEER measurement, mouse colon perfusion American journal of physiology. Cell physiology Medium 30892937
2013 In Drosophila, Atg6 (the BECN1 ortholog) is essential not only for autophagy but also for endocytosis and protein secretion, and is required for normal hematopoiesis. Atg6 mutant flies show enlarged lymph glands, elevated blood cell numbers, and melanotic masses, phenotypes not suppressed by p62 or NFκB mutations, implying these arise from non-autophagy trafficking defects. Drosophila Atg6 null mutant generation, fluorescence and electron microscopy, genetic epistasis with p62 and NFκB mutants Development (Cambridge, England) High 23406899
2011 BEC-1 (C. elegans BECN1 ortholog) is required for retrograde transport from endosomes to the Golgi: bec-1 mutants show mislocalization and degradation of MIG-14/Wntless, reduced RME-8 on endosomal membranes, and accumulation of morphologically abnormal endosomes. BEC-1 also functions in phagosome maturation for apoptotic corpse clearance. C. elegans genetics, GFP reporter trafficking assays, immunofluorescence of endosomal markers, RNAi, corpse clearance assays Autophagy High 21183797
2015 BH3 mimetic ABT-737 induces autophagy in parallel with disruption of BCL2-BECN1 binding in BAX/BAK1-double-deficient cells, demonstrating that BCL2 inhibits autophagy by directly binding BECN1 through a BAX/BAK1-independent mechanism. ABT-737 treatment of BAX/BAK1 double-knockout MEFs and HCT116 cells, BCL2-BECN1 Co-IP, autophagy flux assay Autophagy Medium 25715028
2020 PKD2 forms a protein complex with BECN1 via its coiled-coil domain 1 (CC1). PKD2 overexpression triggers autophagy through increased BECN1 interaction; a Ca2+-channel-deficient PKD2D509V mutant does not induce autophagy and shows diminished BECN1 interaction. Intracellular Ca2+ depletion with BAPTA-AM blunts starvation-induced autophagy and disrupts the PKD2-BECN1 complex. Co-immunoprecipitation, GST pulldown, PKD2 domain mutants, Ca2+ chelation (BAPTA-AM), autophagy flux assays Autophagy Medium 32543276
2024 VCP/p97 is UFMylated on K109 by E3 ligase UFL1; this modification stabilizes BECN1 through ATXN3-mediated deubiquitination and facilitates assembly of the PtdIns3K complex. Expression of UFMylation-defective VCP K109 mutant fails to rescue VCP-depletion-induced autophagy defects. Co-immunoprecipitation, mass spectrometry, ubiquitination/UFMylation assays, mutagenesis, autophagy flux assays Autophagy Medium 38762759
2020 BECN1 knockdown in colorectal cancer cells promotes STAT3 phosphorylation and activates the STAT3 signaling pathway by regulating the interaction between STAT3 and JAK2, an autophagy-independent mechanism that promotes CRC cell motility and invasion. siRNA knockdown, phospho-STAT3 western blot, co-immunoprecipitation of STAT3-JAK2, cell migration/invasion assays, in vivo xenograft Cell death & disease Medium 32358527
2020 BECN1 interacts with USP14 (a deubiquitinase) and Vimentin, and regulates USP14-mediated de-ubiquitination of Vimentin. BECN1 overexpression increases NSCLC cell migration; BECN1 knockdown reduces migration, mediated through K48-linked ubiquitination of Vimentin. Co-immunoprecipitation, ubiquitination assay, siRNA knockdown, overexpression, cell migration assays Cell adhesion & migration Low 31272261
2015 A conserved autophagy-specific domain (ECD/BARA-like) of BECN1 is required for its interaction with APP; deletion of BECN1 residues 285–299 does not impair PIK3C3 interaction or macroautophagy but specifically abolishes APP-BECN1 interaction and BECN1-dependent APP internalization and degradation. BECN1 deletion mutants, co-immunoprecipitation, surface APP internalization assays, lysosomal degradation assays Autophagy Medium 27715386
2014 GABP transcription factor binds to conserved GABP sites in the BECN1 promoter and activates transcription of BECN1 and other BECN1-PIK3C3 complex genes. Nutrient starvation increases GABP-dependent transcriptional activity and GABP recruitment to the BECN1 promoter; GABP knockdown reduces BECN1-PIK3C3 complex protein levels and autophagy. Promoter luciferase assays, ChIP, siRNA knockdown, qPCR, western blot, autophagy flux assays Autophagy Medium 25046113
2020 BECN1 translocates to the nucleus in response to ionizing radiation. Nuclear BECN1 interacts with CDC25C (via residues 89–155) and CHK2 (via residues 151–224), facilitating CHK2-CDC25C interaction and CDC25C phosphorylation, which leads to CDK1 inactivation and G2/M checkpoint arrest. Nuclear fractionation, co-immunoprecipitation with domain mapping, western blot for phospho-CDC25C/CDK1, BECN1 knockdown, irradiation assay Cell death discovery Medium 32802407
2019 SENP3 deSUMOylates BECN1, impairing BECN1-PIK3C3 complex formation and suppressing autophagy. PIAS3 is the SUMO3 E3 ligase that conjugates SUMO3 to BECN1 predominantly at K380; K380 SUMOylation enhances interactions with UVRAG, PIK3C3, and ATG14. SUMO pull-down, Co-IP, Senp3 knockout mice (liver-specific), site-directed mutagenesis of K380, PI3KC3 complex activity assay Autophagy High 31373534

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 629 30057310
2007 Physiological functions of Atg6/Beclin 1: a unique autophagy-related protein. Cell research 490 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 354 9105038
2017 PINK1 and BECN1 relocalize at mitochondria-associated membranes during mitophagy and promote ER-mitochondria tethering and autophagosome formation. Autophagy 295 28368777
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 205 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 173 33977871
2014 Mutational landscape of the essential autophagy gene BECN1 in human cancers. Molecular cancer research : MCR 159 24478461
2018 BECN1 is a new driver of ferroptosis. Autophagy 155 30145930
2005 Characterization of an ERAD gene as VPS30/ATG6 reveals two alternative and functionally distinct protein quality control pathways: one for soluble Z variant of human alpha-1 proteinase inhibitor (A1PiZ) and another for aggregates of A1PiZ. Molecular biology of the cell 153 16267277
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 137 25483966
2022 HucMSC-derived exosomes delivered BECN1 induces ferroptosis of hepatic stellate cells via regulating the xCT/GPX4 axis. Cell death & disease 132 35395830
2017 A Becn1 mutation mediates hyperactive autophagic sequestration of amyloid oligomers and improved cognition in Alzheimer's disease. PLoS genetics 130 28806762
2014 ARRB1/β-arrestin-1 mediates neuroprotection through coordination of BECN1-dependent autophagy in cerebral ischemia. Autophagy 121 24988431
2011 The Atg6/Vps30/Beclin 1 ortholog BEC-1 mediates endocytic retrograde transport in addition to autophagy in C. elegans. Autophagy 104 21183797
2017 Cisplatin induces protective autophagy through activation of BECN1 in human bladder cancer cells. Drug design, development and therapy 101 28553083
2014 BECN1 is involved in the initiation of mitophagy: it facilitates PARK2 translocation to mitochondria. Autophagy 101 24879156
2018 TRIM59 regulates autophagy through modulating both the transcription and the ubiquitination of BECN1. Autophagy 93 30231667
2016 Mechanistic study of TRPM2-Ca(2+)-CAMK2-BECN1 signaling in oxidative stress-induced autophagy inhibition. Autophagy 91 27245989
2017 Plant Bax Inhibitor-1 interacts with ATG6 to regulate autophagy and programmed cell death. Autophagy 89 28537463
2014 Pathogenic role of BECN1/Beclin 1 in the development of amyotrophic lateral sclerosis. Autophagy 88 24905722
2013 Atg6 is required for multiple vesicle trafficking pathways and hematopoiesis in Drosophila. Development (Cambridge, England) 88 23406899
2015 BAX and BAK1 are dispensable for ABT-737-induced dissociation of the BCL2-BECN1 complex and autophagy. Autophagy 85 25715028
2016 Conformational flexibility of BECN1: Essential to its key role in autophagy and beyond. Protein science : a publication of the Protein Society 79 27414988
2015 Divergent roles of BECN1 in LC3 lipidation and autophagosomal function. Autophagy 75 25955014
2018 Bidirectional Control of Autophagy by BECN1 BARA Domain Dynamics. Molecular cell 73 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 70 35422093
2019 A fine-tuning mechanism underlying self-control for autophagy: deSUMOylation of BECN1 by SENP3. Autophagy 62 31373534
2019 KLF5 downregulation desensitizes castration-resistant prostate cancer cells to docetaxel by increasing BECN1 expression and inducing cell autophagy. Theranostics 62 31534497
2017 Phosphorylated CAV1 activates autophagy through an interaction with BECN1 under oxidative stress. Cell death & disease 60 28542134
2010 Co-inhibition of BCL-W and BCL2 restores antiestrogen sensitivity through BECN1 and promotes an autophagy-associated necrosis. PloS one 60 20062536
2016 ABHD5 interacts with BECN1 to regulate autophagy and tumorigenesis of colon cancer independent of PNPLA2. Autophagy 58 27559856
2017 BECN1-dependent CASP2 incomplete autophagy induction by binding to rabies virus phosphoprotein. Autophagy 55 28129024
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 54 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 LncRNA FIRRE functions as a tumor promoter by interaction with PTBP1 to stabilize BECN1 mRNA and facilitate autophagy. Cell death & disease 49 35110535
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
2019 Intestinal epithelial tight junction barrier regulation by autophagy-related protein ATG6/beclin 1. American journal of physiology. Cell physiology 48 30892937
2016 BECN1/Beclin 1 sorts cell-surface APP/amyloid β precursor protein for lysosomal degradation. Autophagy 45 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
2012 Recombinant protein rVP1 upregulates BECN1-independent autophagy, MAPK1/3 phosphorylation and MMP9 activity via WIPI1/WIPI2 to promote macrophage migration. Autophagy 39 23051912
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
2015 SLC9A3R1 stimulates autophagy via BECN1 stabilization in breast cancer cells. Autophagy 37 26218645
2018 TP53 is required for BECN1- and ATG5-dependent cell death induced by sphingosine kinase 1 inhibition. Autophagy 36 29368980
2017 A Non-Cell-Autonomous Role of BEC-1/BECN1/Beclin1 in Coordinating Cell-Cycle Progression and Stem Cell Proliferation during Germline Development. Current biology : CB 36 28285998
2013 BECN1 and BIM interactions with MCL-1 determine fludarabine resistance in leukemic B cells. Cell death & disease 36 23681223
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 33 33953572
2020 p62 is Negatively Implicated in the TRAF6-BECN1 Signaling Axis for Autophagy Activation and Cancer Progression by Toll-Like Receptor 4 (TLR4). Cells 33 32384667
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
2019 Chlorogenic Acid Alleviates Thiram-Induced Tibial Dyschondroplasia by Modulating Caspases, BECN1 Expression and ECM Degradation. International journal of molecular sciences 30 31261680
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
2024 VCP/p97 UFMylation stabilizes BECN1 and facilitates the initiation of autophagy. Autophagy 27 38762759
2020 BECN1 promotes radiation-induced G2/M arrest through regulation CDK1 activity: a potential role for autophagy in G2/M checkpoint. Cell death discovery 26 32802407
2016 The BECN1 N-terminal domain is intrinsically disordered. Autophagy 26 27046249
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
2019 CRBN Is a Negative Regulator of Bactericidal Activity and Autophagy Activation Through Inhibiting the Ubiquitination of ECSIT and BECN1. Frontiers in immunology 24 31620128
2023 Ginsenoside Rb1 induces hepatic stellate cell ferroptosis to alleviate liver fibrosis via the BECN1/SLC7A11 axis. Journal of pharmaceutical analysis 22 38784156
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
2020 AMPKα1 Regulates Lung and Breast Cancer Progression by Regulating TLR4-Mediated TRAF6-BECN1 Signaling Axis. Cancers 22 33172060
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
2023 SIRT3-mediated autophagy contributes to ferroptosis-induced anticancer by inducing the formation of BECN1-SLC7A11 complex. Biochemical pharmacology 21 37196680
2020 Oncogenic role of MIR516A in human bladder cancer was mediated by its attenuating PHLPP2 expression and BECN1-dependent autophagy. Autophagy 21 32116109
2019 Oncogene SRSF3 suppresses autophagy via inhibiting BECN1 expression. Biochemical and biophysical research communications 21 30654935
2017 Catalase ameliorates diabetes-induced cardiac injury through reduced p65/RelA- mediated transcription of BECN1. Journal of cellular and molecular medicine 20 28643395
2024 Overcoming multi-drug resistance in SCLC: a synergistic approach with venetoclax and hydroxychloroquine targeting the lncRNA LYPLAL1-DT/BCL2/BECN1 pathway. Molecular cancer 19 39478582
2023 Propofol suppresses OGD/R-induced ferroptosis in neurons by inhibiting the HIF-1α/YTHDF1/BECN1 axis. Brain injury 18 37614036
2019 BECN1 promotes the migration of NSCLC cells through regulating the ubiquitination of Vimentin. Cell adhesion & migration 18 31272261
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
2019 BCL2L10/BECN1 modulates hepatoma cells autophagy by regulating PI3K/AKT signaling pathway. Aging 16 30696802
2018 BECN1-knockout impairs tumor growth, migration and invasion by suppressing the cell cycle and partially suppressing the epithelial-mesenchymal transition of human triple-negative breast cancer cells. International journal of oncology 16 30015871
2020 Depletion of Adipocyte Becn1 Leads to Lipodystrophy and Metabolic Dysregulation. Diabetes 14 33046512
2020 Silencing ATG6 and PI3K accelerates petal senescence and reduces flower number and shoot biomass in petunia. Plant science : an international journal of experimental plant biology 14 33288020
2014 GA binding protein augments autophagy via transcriptional activation of BECN1-PIK3C3 complex genes. Autophagy 14 25046113

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