Affinage

ATG7

Ubiquitin-like modifier-activating enzyme ATG7 · UniProt O95352

Length
703 aa
Mass
78.0 kDa
Annotated
2026-04-28
100 papers in source corpus 30 papers cited in narrative 30 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

ATG7 is an E1-like ubiquitin-activating enzyme that functions as the central catalyst for two autophagy-specific ubiquitin-like conjugation cascades, activating both ATG8/LC3 (for lipidation to phosphatidylethanolamine on autophagosome membranes) and ATG12 (for conjugation to ATG5) through a conserved catalytic cysteine (C572 in humans) that forms thioester intermediates with both substrates (PMID:23142976, PMID:30503495). Structurally, ATG7 functions as a homodimer in which a unique N-terminal domain recruits the E2-like enzymes ATG3 and ATG10 via noncanonical backside interactions, while flexibly tethered C-terminal domains present E2 active sites to the catalytic cysteine of the opposite protomer for ubiquitin-like protein transfer; ATG7 activity is positively regulated by S-nitrosylation at C402, K63-linked ubiquitination at K45 (by TRIM32) and K413 (by TRIM7), and negatively regulated by p300/CBP-mediated acetylation that disrupts the ATG7–ATG3 interaction (PMID:23142976, PMID:29237558, PMID:36480290, PMID:37943659, PMID:36576150, PMID:37999993). Independent of its enzymatic role, ATG7 directly binds p53 to regulate p21-dependent cell cycle arrest under metabolic stress and interacts with caspase-9 to modulate apoptotic signaling, and in endothelial cells sequesters ZNF148 in the cytoplasm to prevent STAT1-mediated suppression of HIF1A-dependent angiogenesis (PMID:22499945, PMID:24362031, PMID:36300763). Biallelic loss-of-function variants in human ATG7 cause a neurodevelopmental disorder with cerebellar and corpus callosum abnormalities, muscle weakness, and endocrine dysfunction (PMID:34161705).

Mechanistic history

Synthesis pass · year-by-year structured walk · 13 steps
  1. 2004 High

    Establishing that ATG7 is genetically required for autophagic cell death resolved whether autophagy gene products participate in regulated cell death pathways beyond nutrient recycling.

    Evidence ATG7-deficient cells failed to undergo autophagic cell death downstream of caspase-8 inhibition in an RIP/JNK-dependent pathway

    PMID:15131264

    Open questions at the time
    • Mechanism by which ATG7 promotes cell death versus survival was not distinguished
    • Direct molecular targets of ATG7 in the death pathway were not identified
  2. 2009 High

    Demonstration of an ATG5/ATG7-independent macroautophagy pathway defined ATG7-dependent LC3 lipidation as the hallmark of canonical autophagy and revealed that alternative autophagosome biogenesis can bypass ATG7.

    Evidence Atg5/Atg7 KO mouse cells showed Rab9-dependent autophagosome formation without LC3 lipidation by electron microscopy

    PMID:19794493

    Open questions at the time
    • Whether ATG7-independent autophagy compensates for ATG7 loss in all tissues was unknown
    • Relative physiological importance of the two pathways was unresolved
  3. 2011 High

    Conditional deletion of Atg7 in hematopoietic cells revealed that ATG7-dependent autophagy is essential for mitochondrial quality control and maintenance of hematopoietic stem cells, linking ATG7 to mitophagy in a defined stem cell population.

    Evidence Hematopoietic-specific Atg7 KO mice showed mitochondrial accumulation, ROS increase, myeloproliferation, and failure of HSC reconstitution

    PMID:21339326

    Open questions at the time
    • Whether ATG7's mitophagy role was enzymatic or scaffolding was not tested
    • Specific mitophagy receptors engaged by ATG7 in HSCs were not identified
  4. 2012 High

    Crystal structures of the Atg7 homodimer in complex with E2 enzymes Atg3 and Atg10 revealed an unprecedented trans-active E1 architecture where one protomer recruits the E2 while the opposite protomer provides the catalytic cysteine, solving how a single E1 services two distinct conjugation cascades.

    Evidence X-ray crystallography of yeast (Atg7–Atg3)₂ and (Atg7–Atg10)₂ with mutational validation; catalytic C572S mutant trapping in human cells

    PMID:23142976 PMID:30503495

    Open questions at the time
    • Full-length human ATG7 structure was not determined
    • Structural basis for substrate (ATG8 vs ATG12) discrimination by the same catalytic site remained unclear
  5. 2012 High

    Discovery that ATG7 directly binds p53 to drive p21 transcription and cell cycle arrest independently of its E1 activity established a non-autophagic, scaffolding role for ATG7 in the DNA damage response.

    Evidence Reciprocal Co-IP of ATG7–p53; catalytic-dead ATG7 mutant rescued cell cycle arrest in Atg7-KO MEFs; Chk2 epistasis in vivo

    PMID:22499945

    Open questions at the time
    • Structural basis of the ATG7–p53 interaction was not defined
    • Whether p53 binding competes with E2 binding on ATG7 was unknown
  6. 2013 Medium

    Identification of a direct ATG7–caspase-9 complex in which ATG7 suppresses caspase-9 apoptotic activity while catalytic-dead caspase-9 facilitates LC3-II formation revealed bidirectional crosstalk between autophagy and apoptosis converging on ATG7.

    Evidence Endogenous Co-IP of ATG7–caspase-9; catalytic-dead caspase-9 mutant promoted LC3-II; ATG7 overexpression suppressed caspase-9 activity

    PMID:24362031

    Open questions at the time
    • Not independently replicated outside one laboratory
    • Binding interface and stoichiometry of ATG7–caspase-9 were not determined
    • In vivo relevance not tested
  7. 2014 High

    BAT3 was shown to limit p300-dependent acetylation of ATG7 by controlling p300 nuclear localization, establishing acetylation as a negative regulatory modification of ATG7.

    Evidence BAT3-KO MEFs showed ATG7 hyperacetylation and reduced autophagy; cytosol-restricted BAT3 mutant rescued

    PMID:24591579

    Open questions at the time
    • Specific acetylation sites on ATG7 were not mapped in this study
    • Whether acetylation affects ATG12 conjugation in addition to LC3 lipidation was not tested
  8. 2017 High

    Structural determination of the ATG8–ATG7 C-terminal domain complex revealed that ATG8 binds a site distinct from the catalytic cysteine, inducing conformational activation of an autoinhibited crossover loop, solving how substrate binding allosterically triggers the E1 activation reaction.

    Evidence X-ray crystallography of Atg8–Atg7(CTD) with mutagenesis confirming functional relevance

    PMID:29237558

    Open questions at the time
    • Whether ATG12 binding induces a similar allosteric activation was unknown
    • Dynamics of the conformational switch were not captured
  9. 2018 High

    Post-transcriptional control of ATG7 levels by CCR4-NOT deadenylase-mediated shortening of ATG7 mRNA poly(A) tails was shown to prevent pathological ATG7–p53 interaction and lethal cardiomyopathy, revealing that ATG7 abundance must be tightly controlled to prevent non-autophagic cell death.

    Evidence Cnot3-KO mice showed lengthened ATG7 mRNA poly(A) tails, elevated ATG7 protein, ATG7–p53 complex formation, and heart failure rescued by Atg7 ablation but not Atg5 ablation

    PMID:29438013

    Open questions at the time
    • Whether other deadenylase complexes target ATG7 mRNA was not tested
    • Tissue-specificity of this regulatory axis beyond heart was not explored
  10. 2019 High

    TP53INP2 was identified as a scaffold that bridges ATG7 and LC3B into a ternary complex to promote LC3 lipidation, revealing a cofactor that enhances E1-substrate encounter.

    Evidence Reciprocal Co-IP and GST pulldown of LC3B–TP53INP2–ATG7; LIR mutants disrupted complex and reduced LC3-PE production

    PMID:30767704

    Open questions at the time
    • Whether TP53INP2 is required in all cell types or only specific contexts was unclear
    • Effect on ATG12 conjugation was not examined
  11. 2021 High

    Identification of biallelic ATG7 loss-of-function variants in patients with a neurodevelopmental syndrome (cerebellar/corpus callosum abnormalities, myopathy, endocrine defects) established ATG7 as a human disease gene and demonstrated that near-complete loss of autophagic flux is compatible with survival but causes multisystem pathology.

    Evidence Five families with biallelic ATG7 variants; patient fibroblasts and muscle showed impaired autophagic sequestration; deleterious variants failed to complement in yeast and MEF assays

    PMID:34161705

    Open questions at the time
    • Genotype–phenotype correlation across different variant types is limited by small patient numbers
    • Whether residual ATG7-independent autophagy modulates disease severity was not tested
  12. 2022 High

    In endothelial cells, ATG7 was found to sequester ZNF148 in the cytoplasm independently of autophagy, preventing STAT1 transcription and thereby maintaining HIF1A-dependent angiogenesis — a second major non-autophagic scaffolding function.

    Evidence Endothelial-specific Atg7 KO mice; Co-IP of ATG7–ZNF148; ChIP of ZNF148 at STAT1 promoter; HIF1A overexpression and fludarabine rescue

    PMID:36300763

    Open questions at the time
    • Whether ATG7's enzymatic domain or NTD mediates ZNF148 binding was not mapped
    • Relevance beyond ischemic angiogenesis not explored
  13. 2023 High

    Three distinct post-translational regulatory inputs to ATG7 were mapped in a single year: Trx1-mediated S-nitrosylation at C402 stimulates E1 activity, TRIM32-mediated K63-ubiquitination at K45 downstream of ATM–CHK2 initiates autophagy under oxidative stress, TRIM7-mediated K63-ubiquitination at K413 promotes autophagy during infection, and p300/CBP acetylation disrupts ATG7–ATG3 interaction to inhibit both macroautophagy and LC3-associated microautophagy.

    Evidence C402S knock-in mice and in vitro transnitrosylation reconstitution; Chk2-KO mice with site-specific ubiquitination mapping; TRIM7-KO cells/mice with K413 mutant; in vitro LC3 lipidation with acetylated/deacetylated ATG7

    PMID:36480290 PMID:36576150 PMID:37943659 PMID:37999993

    Open questions at the time
    • Crosstalk between these modifications (e.g., whether ubiquitination and acetylation are mutually exclusive) was not tested
    • Structural consequences of each modification on ATG7 conformation are unknown
    • Whether S-nitrosylation at C402 is relevant outside cardiac ischemia is untested

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key unresolved questions include: (1) the full-length human ATG7 structure in its apo- and substrate-bound states, (2) how ATG7 discriminates between ATG8 and ATG12 substrates, (3) whether the non-autophagic functions (p53 binding, ZNF148 sequestration, caspase-9 modulation, succinate metabolism) operate through shared or independent structural surfaces, and (4) how ATG7 post-translational modifications are integrated to set autophagic flux in different tissues.
  • No full-length human ATG7 crystal or cryo-EM structure
  • Substrate selectivity mechanism unresolved
  • Integration of multiple PTMs not tested in a single system

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140657 ATP-dependent activity 4 GO:0098772 molecular function regulator activity 3 GO:0140096 catalytic activity, acting on a protein 3
Localization
GO:0005829 cytosol 3
Pathway
R-HSA-9612973 Autophagy 10 R-HSA-5357801 Programmed Cell Death 5 R-HSA-392499 Metabolism of proteins 3 R-HSA-1640170 Cell Cycle 2 R-HSA-168256 Immune System 1
Partners
ATG10ATG12ATG3CASP9LC3BTP53TP53INP2ZNF148
Complex memberships
ATG7 homodimerATG7–ATG10 E1-E2 complexATG7–ATG3 E1-E2 complex

Evidence

Reading pass · 30 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2012 Crystal structures of yeast (Atg7-Atg3)₂ and (Atg7-Atg10)₂ complexes revealed that Atg7's unique N-terminal domain recruits distinctive elements from the Atg3 and Atg10 'backsides' (noncanonical multisite E1-E2 recognition), and flexibly tethered E1 domains present 'frontside' E2 active sites to the catalytic cysteine in the C-terminal domain from the opposite Atg7 protomer in the homodimer, juxtaposing E1 and E2 catalytic cysteines for UBL transfer. X-ray crystallography of yeast Atg7-Atg3 and Atg7-Atg10 complexes combined with mutational analysis Nature structural & molecular biology High 23142976
2017 Crystal structure of Atg8 bound to the C-terminal domain of Atg7 revealed an unprecedented binding mode in which Atg8 contacts the C-terminal α-helix and crossover loop of Atg7 (not the central β-sheet or catalytic site), inducing a conformational change from the autoinhibited crossover loop to an active conformation; mutational analyses confirmed this interaction is important for the activation reaction. X-ray crystallography of Atg8-Atg7(CTD) complex combined with mutational analysis Journal of molecular biology High 29237558
2012 Atg7 acts as an E1-like activating enzyme that mediates both LC3-phosphatidylethanolamine (Atg8) and ATG12 conjugation reactions; the catalytic cysteine at position 572 (human) forms a thioester bond with LC3 or ATG12, and a C572S mutant forms stable intermediate complexes that block both conjugation pathways and suppress autophagosome formation. Active-site mutagenesis (C572S substitution) in TetOff cells; Western blot and autophagosome assays Biochemical and biophysical research communications High 23142976 30503495
2004 ATG7 is required for autophagic cell death downstream of caspase-8 inhibition; in a pathway activated by receptor-interacting protein kinase and JNK, ATG7 and beclin 1 are genetically required for cell death with autophagic morphology. Genetic loss-of-function (ATG7-deficient cells) combined with pharmacological caspase-8 inhibition; cell death morphology assays Science High 15131264
2009 Atg5/Atg7-dependent conventional macroautophagy involves LC3 lipidation; an alternative Atg5/Atg7-independent macroautophagy pathway exists that generates autophagosomes via Rab9-dependent fusion of isolation membranes with trans-Golgi and late endosome vesicles without LC3 lipidation, demonstrating that LC3 lipidation is an ATG7-dependent step specific to canonical autophagy. Atg5 and Atg7 knockout mouse cells; electron microscopy; LC3 lipidation assays; Rab9 dominant-negative experiments Nature High 19794493
2012 Independent of its E1-like enzymatic activity, Atg7 binds directly to the tumor suppressor p53 to regulate transcription of p21(CDKN1A), thereby mediating cell cycle arrest during nutrient starvation; Atg7-deficient MEFs fail to arrest and show augmented DNA damage with p53-dependent apoptosis under prolonged metabolic stress. Atg7-knockout MEFs; co-immunoprecipitation of Atg7-p53 complex; enzymatic-activity-dead Atg7 mutant rescue experiments; genetic deletion of Chk2 in Atg7−/− mice Science High 22499945
2014 BAT3 controls p300-dependent acetylation of ATG7; BAT3 limits p300 access to ATG7 in the cytosol by regulating p300 nuclear localization. In the absence of BAT3, ATG7 is hyperacetylated by p300, which inhibits autophagy; BAT3 also increases p53 acetylation to promote pro-autophagic p53 target gene expression. BAT3−/− mouse embryos and MEFs; acetylation assays; subcellular fractionation; BAT3 cytosol-restricted mutant experiments PNAS High 24591579
2013 Caspase-9 forms a direct protein complex with Atg7; Atg7 represses the apoptotic activity of caspase-9 through this interaction (independently of autophagy), while caspase-9 (independently of its catalytic activity) facilitates Atg7-mediated LC3-II formation; Atg7 is not a direct proteolytic substrate of caspase-9. Co-immunoprecipitation of endogenous Atg7-caspase-9 complex; catalytic-dead caspase-9 mutant; Atg7 overexpression/knockdown with apoptosis and LC3-II readouts Journal of Biological Chemistry Medium 24362031
2023 Thioredoxin 1 (Trx1) transnitrosylates Atg7 at Cys402 during myocardial ischemia: oxidized Trx1 (Cys32-Cys35 disulfide) undergoes thiol-disulfide exchange with Atg7 Cys545-Cys548, releasing NO from Trx1 Cys73 which is then transferred to Atg7 Cys402; S-nitrosylation of Atg7 at Cys402 stimulates its E1-like activity and promotes autophagy. Atg7 C402S knock-in mice; in vitro transnitrosylation assays; thiol-disulfide exchange biochemistry; ischemia model Journal of Clinical Investigation High 36480290
2023 Under oxidative stress, ATM phosphorylates CHK2 at T68, which phosphorylates the E3 ligase TRIM32 at S55; TRIM32 then mediates K63-linked ubiquitination of ATG7 at K45 to initiate autophagy. Chk2−/− mice show reduced TRIM32 phosphorylation and reduced ATG7 ubiquitination and aggravated brain infarction. ATM-CHK2 pathway knockouts; site-specific phosphorylation and ubiquitination mapping; Chk2−/− stroke mouse model Cell Reports High 37943659
2023 TRIM7/RNF90 (a RING-type E3 ligase) promotes K63-linked ubiquitination of ATG7 at K413, positively regulating autophagosome accumulation and autophagy during L. monocytogenes infection and starvation; TRIM7 deficiency reduces autophagy and increases innate immune signaling. TRIM7 KO cells/mice; site-specific ubiquitination assay (K413 mutant); proximity ligation assay; infection models Autophagy High 36576150
2023 Acetylation of ATG7 by p300/CBP disrupts its interaction with the E2-like enzyme ATG3, inhibiting LC3 lipidation and both macroautophagy and LC3-associated microautophagy; deacetylation of ATG7 (by sirtuins) in response to stimuli (starvation, cGAMP, EGF) is required to induce these processes and enable elimination of cytoplasmic DNA and degradation of lysosome membrane proteins. In vitro LC3 lipidation assays with acetylated/deacetylated ATG7; ATG7-ATG3 interaction assays; MEF KO rescue experiments; deacetylase inhibitor/activator treatments Autophagy High 37999993
2019 TP53INP2 promotes autophagosome biogenesis by directly interacting with ATG7 and LC3B in the cytoplasm to form a LC3B-TP53INP2-ATG7 ternary complex; loss of TP53INP2-ATG7 or TP53INP2-LC3 interaction significantly reduces LC3B-ATG7 binding and LC3B-PE production. Co-immunoprecipitation; GST pulldown; LIR/interaction domain mutants; LC3B-PE lipidation assays; confocal co-localization Autophagy High 30767704
2022 In endothelial cells, ATG7 interacts with the transcription factor ZNF148/ZBP-89 in the cytoplasm, preventing ZNF148 nuclear translocation. Loss of endothelial Atg7 dissociates this complex, enabling ZNF148 to bind importin KPNB1 and translocate to the nucleus where it drives STAT1 transcription; elevated STAT1 then suppresses HIF1A expression, impairing ischemia-induced angiogenesis independently of autophagy. Endothelial-specific Atg7 KO mice; Co-IP of Atg7-ZNF148 complex; ChIP for STAT1 on HIF1A promoter; HIF1A overexpression rescue; STAT1 inhibitor (fludarabine) rescue Autophagy High 36300763
2023 Endothelial ATG7 promotes fibronectin expression via PKA/CREB phosphorylation signaling; loss of endothelial Atg7 reduces PKA activity and CREB phosphorylation, decreasing fibronectin production in the basement membrane, which causes astrocyte endfeet detachment from microvessels and blood-brain barrier leakage. Endothelial-specific Atg7 KO mice; PKA activity assay; CREB phosphorylation Western blot; fibronectin immunostaining; BBB permeability assays Journal of Cell Biology Medium 36995368
2018 Control of Atg7 mRNA poly(A) tail length by the CCR4-NOT deadenylase complex (via Cnot3 subunit) posttranscriptionally limits Atg7 protein levels; loss of Cnot3 increases Atg7 expression, causing Atg7 to interact with p53 and induce expression of cell death-promoting genes in cardiomyocytes leading to lethal heart failure. Genetic ablation of Atg7 (but not Atg5) rescued cardiac function in Cnot1/Cnot3 KO mice. Conditional Cnot1/Cnot3 KO mice; poly(A) tail assay; Atg7 genetic ablation rescue; Co-IP of Atg7-p53; gene expression analysis Science Signaling High 29438013
2018 Atg7 mediates vancomycin-induced renal tubular cell apoptosis by binding to PKC-δ; PT-specific Atg7 KO mice are protected from vancomycin nephrotoxicity, and this protection is abolished by re-expression of myc-tagged PKCδ. ATG7 upregulates PKC-δ expression among cell-death genes activated during vancomycin treatment. Proximal tubule-specific Atg7 KO mice; global gene expression analysis; Co-IP of Atg7-PKCδ; PKCδ inhibitor experiments; myc-PKCδ rescue FASEB Journal Medium 30589566
2011 Conditional deletion of Atg7 in the hematopoietic system leads to loss of HSC function, accumulation of mitochondria and ROS in stem/progenitor cells, increased proliferation and DNA damage, myeloproliferation, and death; Atg7-deficient LSK cells fail to reconstitute hematopoiesis, demonstrating that Atg7-dependent autophagy is essential for mitochondrial quality control and HSC maintenance. Conditional Atg7 KO in hematopoietic system (Mx-Cre); flow cytometry; transplantation assays; mitochondria and ROS quantification Journal of Experimental Medicine High 21339326
2011 Atg7 overexpression induces basal autophagy and rescues the autophagic deficiency in CryAB-R120G cardiomyopathy cells, reducing preamyloid oligomers, aggregate content, and cytotoxicity; conversely, Atg7 siRNA knockdown further reduces autophagy and increases aggregates and cytotoxicity in CryAB-R120G cells. Adenoviral Atg7 overexpression and siRNA knockdown in neonatal rat cardiomyocytes; autophagic flux assays; aggregate quantification Circulation Research Medium 21617129
2010 shRNA knockdown of Atg7 (but not Beclin1) significantly inhibits lysosome dysfunction-induced neural precursor cell death and caspase-3 activation, identifying Atg7 as an upstream mediator of lysosome dysfunction-triggered apoptosis; in contrast, both Atg7 and Beclin1 knockdown inhibit starvation-induced autophagosome accumulation, and Atg7 knockdown has no effect on starvation-induced death. shRNA knockdown of Atg7 vs Beclin1 in neural precursor cells; chloroquine/bafilomycin A1 lysosomal damage model; caspase-3 activation and cell death assays Journal of Biological Chemistry Medium 20123985
2021 Loss of Atg7 in intestinal stem cells (Lgr5+ISC) induces p53-mediated apoptosis driven by increasing oxidative stress, alterations in microbiota interactions, and defective DNA repair; p53 deletion prevents death of Atg7-deficient ISCs but promotes genetic instability and tumor formation, placing Atg7 upstream of p53 in the ISC stress-response pathway. Conditional Atg7 KO in intestinal epithelium and specifically in Lgr5+ ISCs; p53 co-deletion epistasis; ROS measurements; DNA damage assays; irradiation experiments PNAS High 32371487
2021 METTL3-mediated m6A modification of ATG7 mRNA decreases ATG7 mRNA stability, reducing ATG7 protein expression and thereby impairing autophagosome formation in fibroblast-like synoviocytes; this impaired autophagy leads to GATA4 upregulation and SASP, promoting cellular senescence in osteoarthritis. m6A methylated RNA immunoprecipitation; RNA immunoprecipitation; METTL3 siRNA KD; mRNA stability assays; autophagy flux measurements in OA patient FLS and mouse DMM model Annals of the Rheumatic Diseases Medium 34706873
2019 FTO (m6A demethylase) directly targets Atg5 and Atg7 transcripts; FTO silencing increases m6A levels on ATG7 mRNA, enabling YTHDF2 capture and mRNA degradation, reducing ATG7 protein expression and inhibiting autophagosome formation and adipogenesis; adipose-specific FTO KO mice show decreased ATG5/ATG7-dependent autophagy. MeRIP-qPCR; RNA-immunoprecipitation for YTHDF2-ATG7 interaction; FTO KD/KO; adipose-selective FTO KO mice; autophagy flux assays Autophagy Medium 31451060
2022 ATG7 promotes tumor cell invasion and metastasis in pancreatic ductal adenocarcinoma through a mechanism independent of autophagy: Atg7+/− tumors have lower succinate levels and reduced invasiveness; ectopic ATG7 re-expression in Atg7+/− cells rescues invasion without changing autophagic capacity; cell-permeable succinate also rescues invasion. Atg7 hemizygous PDAC mouse model; metabolomics (succinate); invasion assays; ATG7 re-expression in Atg7+/− cells; cell-permeable succinate rescue PNAS Medium 35867735
2020 ANXA2 (annexin A2) upregulates ATG7 transcription in TNBC cells via MTORC2-dependent phosphorylation of HSF1, which then acts as a transcriptional activator at the ATG7 promoter; ANXA2 knockdown reduces ATG7 expression, autophagic flux, and chemoresistance to doxorubicin. ANXA2 KD; HSF1 phosphorylation assays; ChIP for HSF1 on ATG7 promoter; MTORC2 inhibition; xenograft mouse model Autophagy Medium 38290972
2020 ATG7 loss in outer hair cells disrupts mitochondrial quality control (mitophagy), causing accumulation of dysfunctional mitochondria, stereocilium damage, somatic electromotility disturbances, and presynaptic ribbon degeneration, ultimately leading to OHC loss and hearing impairment; ATG7-independent autophagy cannot compensate. OHC-specific Atg7 conditional KO mice; electrophysiology (electromotility); transmission electron microscopy; auditory function tests Cell Death & Disease Medium 33099575
2023 In human iPSC-derived macrophages, ATG7 (deleted by CRISPR-Cas9) is required to restrict cytosolic Mtb replication: ATG7 deletion increased replication of WT Mtb but not of Mtb ΔesxBA (unable to escape phagosome), indicating ATG7-dependent canonical autophagy targets cytosolic bacteria specifically. CRISPR-Cas9 deletion of ATG7 in iPSDM; Mtb mutant panel; single-cell high-content imaging of bacterial replication Nature Microbiology Medium 36959508
2021 Biallelic loss-of-function variants in human ATG7 cause impaired autophagic flux and a neurodevelopmental disorder with cerebellar/corpus callosum abnormalities, muscle, and endocrine involvement; patient fibroblasts and muscle show markedly reduced autophagic sequestration but preserved basal autophagy evidence; complementation with deleterious ATG7 variants in yeast and MEFs showed poor or absent autophagic function versus wild-type ATG7. Human genetics (5 families); patient-derived fibroblasts and skeletal muscle; autophagic flux assays; yeast and MEF complementation with disease variants New England Journal of Medicine High 34161705
2018 Control of autophagosome size and number by Atg7 in yeast: limiting amounts of Atg7 produce autophagosomes that are both smaller and fewer than normal, suggesting Atg7 has an Atg8-independent role in autophagosome initiation in addition to its Atg8-dependent role in expansion. Yeast Atg7 limiting-expression experiments; electron microscopy measurement of autophagosome size and number; statistical simulation of autophagic body counts Biochemical and biophysical research communications Medium 29906462
2022 ATG7-dependent autophagy degrades NANOG via selective autophagy receptor SQSTM1/p62 (which translocates to the nucleus and associates with K63-ubiquitinated NANOG) during ESC exit from naive pluripotency; loss of ATG7 causes NANOG accumulation, impairs decommissioning of naive enhancers, and disrupts peri-implantation development and neuronal differentiation in vivo. ATG7-depleted ESCs; ATAC-seq and RNA-seq; nuclear SQSTM1 localization; K63-ubiquitinated NANOG Co-IP; in vivo ATG7 depletion embryo analysis Autophagy Medium 35311460

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2004 Regulation of an ATG7-beclin 1 program of autophagic cell death by caspase-8. Science (New York, N.Y.) 1063 15131264
2009 Discovery of Atg5/Atg7-independent alternative macroautophagy. Nature 925 19794493
2011 The autophagy protein Atg7 is essential for hematopoietic stem cell maintenance. The Journal of experimental medicine 508 21339326
2019 m6A mRNA methylation controls autophagy and adipogenesis by targeting Atg5 and Atg7. Autophagy 316 31451060
2021 METTL3-mediated m6A modification of ATG7 regulates autophagy-GATA4 axis to promote cellular senescence and osteoarthritis progression. Annals of the rheumatic diseases 313 34706873
2012 Atg7 modulates p53 activity to regulate cell cycle and survival during metabolic stress. Science (New York, N.Y.) 283 22499945
2015 Atg7 Overcomes Senescence and Promotes Growth of BrafV600E-Driven Melanoma. Cancer discovery 180 25673642
2021 Emerging roles of ATG7 in human health and disease. EMBO molecular medicine 154 34725936
2013 Uba1 functions in Atg7- and Atg3-independent autophagy. Nature cell biology 153 23873149
2011 Atg7 induces basal autophagy and rescues autophagic deficiency in CryABR120G cardiomyocytes. Circulation research 151 21617129
2017 Atg7 Deficiency Intensifies Inflammasome Activation and Pyroptosis in Pseudomonas Sepsis. Journal of immunology (Baltimore, Md. : 1950) 144 28258192
2016 Neuroprotection by selective neuronal deletion of Atg7 in neonatal brain injury. Autophagy 139 26727396
2021 Developmental Consequences of Defective ATG7-Mediated Autophagy in Humans. The New England journal of medicine 138 34161705
2017 Molecular mechanisms and physiological roles of Atg5/Atg7-independent alternative autophagy. Proceedings of the Japan Academy. Series B, Physical and biological sciences 136 28603209
2016 The long noncoding RNA HOTAIR activates autophagy by upregulating ATG3 and ATG7 in hepatocellular carcinoma. Molecular bioSystems 135 27301338
2019 ATG5 and ATG7 induced autophagy interplays with UPR via PERK signaling. Cell communication and signaling : CCS 134 31060556
2019 KCNQ1OT1 promotes autophagy by regulating miR-200a/FOXO3/ATG7 pathway in cerebral ischemic stroke. Aging cell 112 30945454
2016 Atg7 suppression enhances chemotherapeutic agent sensitivity and overcomes stroma-mediated chemoresistance in acute myeloid leukemia. Blood 110 27268264
2015 Atg7 in development and disease: panacea or Pandora's Box? Protein & cell 95 26404030
2017 Autophagy gene ATG7 regulates ultraviolet radiation-induced inflammation and skin tumorigenesis. Autophagy 94 28933598
2012 Noncanonical E2 recruitment by the autophagy E1 revealed by Atg7-Atg3 and Atg7-Atg10 structures. Nature structural & molecular biology 93 23142976
2013 A Complex between Atg7 and Caspase-9: A NOVEL MECHANISM OF CROSS-REGULATION BETWEEN AUTOPHAGY AND APOPTOSIS. The Journal of biological chemistry 92 24362031
2016 ATG7 regulates energy metabolism, differentiation and survival of Philadelphia-chromosome-positive cells. Autophagy 89 27168493
2016 TRIM31 promotes Atg5/Atg7-independent autophagy in intestinal cells. Nature communications 89 27216961
2017 Co-delivery of autophagy inhibitor ATG7 siRNA and docetaxel for breast cancer treatment. Journal of controlled release : official journal of the Controlled Release Society 84 28987884
2019 MiRNA-192-5p attenuates airway remodeling and autophagy in asthma by targeting MMP-16 and ATG7. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 83 31918268
2012 ATG7 deficiency suppresses apoptosis and cell death induced by lysosomal photodamage. Autophagy 82 22889762
2010 Obatoclax induces Atg7-dependent autophagy independent of beclin-1 and BAX/BAK. Cell death & disease 81 21368880
2016 microRNA-20a Inhibits Autophagic Process by Targeting ATG7 and ATG16L1 and Favors Mycobacterial Survival in Macrophage Cells. Frontiers in cellular and infection microbiology 76 27803889
2014 BAT3 modulates p300-dependent acetylation of p53 and autophagy-related protein 7 (ATG7) during autophagy. Proceedings of the National Academy of Sciences of the United States of America 76 24591579
2022 Autophagic Schwann cells promote perineural invasion mediated by the NGF/ATG7 paracrine pathway in pancreatic cancer. Journal of experimental & clinical cancer research : CR 73 35109895
2020 Disruption of Atg7-dependent autophagy causes electromotility disturbances, outer hair cell loss, and deafness in mice. Cell death & disease 71 33099575
2018 ATG7 and ATG9A loss-of-function variants trigger autophagy impairment and ovarian failure. Genetics in medicine : official journal of the American College of Medical Genetics 70 30224786
2017 Apigenin sensitizes hepatocellular carcinoma cells to doxorubic through regulating miR-520b/ATG7 axis. Chemico-biological interactions 70 29191453
2010 Lysosome dysfunction triggers Atg7-dependent neural apoptosis. The Journal of biological chemistry 69 20123985
2019 TP53INP2 contributes to autophagosome formation by promoting LC3-ATG7 interaction. Autophagy 67 30767704
2016 Autophagy Proteins ATG5 and ATG7 Are Essential for the Maintenance of Human CD34(+) Hematopoietic Stem-Progenitor Cells. Stem cells (Dayton, Ohio) 66 26930546
2018 Trophoblast-Specific Conditional Atg7 Knockout Mice Develop Gestational Hypertension. The American journal of pathology 61 30165042
2023 ATG7 and ATG14 restrict cytosolic and phagosomal Mycobacterium tuberculosis replication in human macrophages. Nature microbiology 59 36959508
2018 The CCR4-NOT deadenylase complex controls Atg7-dependent cell death and heart function. Science signaling 59 29438013
2020 Circ-ADAM9 targeting PTEN and ATG7 promotes autophagy and apoptosis of diabetic endothelial progenitor cells by sponging mir-20a-5p. Cell death & disease 58 32661238
2014 Atg7- and Keap1-dependent autophagy protects breast cancer cell lines against mitoquinone-induced oxidative stress. Oncotarget 56 24681637
2020 Essential role for autophagy protein ATG7 in the maintenance of intestinal stem cell integrity. Proceedings of the National Academy of Sciences of the United States of America 54 32371487
2018 Atg7 mediates renal tubular cell apoptosis in vancomycin nephrotoxicity through activation of PKC-δ. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 48 30589566
2017 IL-17A induces autophagy and promotes microglial neuroinflammation through ATG5 and ATG7 in intracerebral hemorrhage. Journal of neuroimmunology 45 28778418
2013 Genetic analysis of the ATG7 gene promoter in sporadic Parkinson's disease. Neuroscience letters 43 23295909
2016 miR-106a suppresses tumor cells death in colorectal cancer through targeting ATG7. Medical molecular morphology 42 27981410
2019 LncRNA CCAT1 promotes autophagy via regulating ATG7 by sponging miR-181 in hepatocellular carcinoma. Journal of cellular biochemistry 40 31218739
2015 Identification of a lung cancer cell line deficient in atg7-dependent autophagy. Autophagy 39 26090719
2020 RNA-binding protein HuR suppresses senescence through Atg7 mediated autophagy activation in diabetic intervertebral disc degeneration. Cell proliferation 38 33372336
2018 Long noncoding RNA NBAT1 inhibits autophagy via suppression of ATG7 in non-small cell lung cancer. American journal of cancer research 37 30323972
2024 ANXA2 (annexin A2) is crucial to ATG7-mediated autophagy, leading to tumor aggressiveness in triple-negative breast cancer cells. Autophagy 35 38290972
2017 miR-96-5p prevents hepatic stellate cell activation by inhibiting autophagy via ATG7. Journal of molecular medicine (Berlin, Germany) 35 29051972
2016 MAPK1/3 regulate hepatic lipid metabolism via ATG7-dependent autophagy. Autophagy 35 26760678
2021 Silencing of ATG2 and ATG7 promotes programmed cell death in wheat via inhibition of autophagy under salt stress. Ecotoxicology and environmental safety 34 34509161
2013 Structures of Atg7-Atg3 and Atg7-Atg10 reveal noncanonical mechanisms of E2 recruitment by the autophagy E1. Autophagy 32 23388412
2020 LncRNA SNHG3 promotes autophagy-induced neuronal cell apoptosis by acting as a ceRNA for miR-485 to up-regulate ATG7 expression. Metabolic brain disease 31 32860611
2017 Atg7 Activates an Autophagy-Essential Ubiquitin-like Protein Atg8 through Multi-Step Recognition. Journal of molecular biology 31 29237558
2024 FTO attenuates LPS-induced acute kidney injury by inhibiting autophagy via regulating SNHG14/miR-373-3p/ATG7 axis. International immunopharmacology 30 38215656
2021 MicroRNA-106a Inhibits Autophagy Process and Antimicrobial Responses by Targeting ULK1, ATG7, and ATG16L1 During Mycobacterial Infection. Frontiers in immunology 29 33505399
2019 Upregulation of ATG7 attenuates motor neuron dysfunction associated with depletion of TARDBP/TDP-43. Autophagy 29 31242080
2017 miR-96 attenuates status epilepticus-induced brain injury by directly targeting Atg7 and Atg16L1. Scientific reports 28 28860495
2024 Insights on E1-like enzyme ATG7: functional regulation and relationships with aging-related diseases. Communications biology 26 38553562
2023 TRIM7/RNF90 promotes autophagy via regulation of ATG7 ubiquitination during L. monocytogenes infection. Autophagy 26 36576150
2023 ATM-CHK2-TRIM32 axis regulates ATG7 ubiquitination to initiate autophagy under oxidative stress. Cell reports 26 37943659
2022 Ablation of endothelial Atg7 inhibits ischemia-induced angiogenesis by upregulating Stat1 that suppresses Hif1a expression. Autophagy 26 36300763
2017 Endothelial-specific deletion of autophagy-related 7 (ATG7) attenuates arterial thrombosis in mice. The Journal of thoracic and cardiovascular surgery 26 28400112
2022 Celastrol upregulated ATG7 triggers autophagy via targeting Nur77 in colorectal cancer. Phytomedicine : international journal of phytotherapy and phytopharmacology 25 35752079
2020 CD13 Induces Autophagy to Promote Hepatocellular Carcinoma Cell Chemoresistance Through the P38/Hsp27/CREB/ATG7 Pathway. The Journal of pharmacology and experimental therapeutics 25 32571958
2015 MIR137 Regulates Starvation-Induced Autophagy by Targeting ATG7. Journal of molecular neuroscience : MN 25 25687327
2021 6-Gingerol relieves myocardial ischaemia/reperfusion injury by regulating lncRNA H19/miR-143/ATG7 signaling axis-mediated autophagy. Laboratory investigation; a journal of technical methods and pathology 24 33758383
2020 Knockdown of Atg7 Induces Nuclear-LC3 Dependent Apoptosis and Augments Chemotherapy in Colorectal Cancer Cells. International journal of molecular sciences 24 32046105
2020 The long noncoding RNA-H19/miRNA-93a/ATG7 axis regulates the sensitivity of pituitary adenomas to dopamine agonists. Molecular and cellular endocrinology 24 32946927
2020 MicroRNA-143 sensitizes acute myeloid leukemia cells to cytarabine via targeting ATG7- and ATG2B-dependent autophagy. Aging 24 33077697
2020 Discovery and optimization of pyrazolopyrimidine sulfamates as ATG7 inhibitors. Bioorganic & medicinal chemistry 23 32912429
2018 MiR-490-3p inhibits autophagy via targeting ATG7 in hepatocellular carcinoma. IUBMB life 23 29676845
2020 Absence of Atg7 in the liver disturbed hepatic regeneration after liver injury. Liver international : official journal of the International Association for the Study of the Liver 22 32141704
2023 Thioredoxin 1 promotes autophagy through transnitrosylation of Atg7 during myocardial ischemia. The Journal of clinical investigation 21 36480290
2023 Endothelial depletion of Atg7 triggers astrocyte-microvascular disassociation at blood-brain barrier. The Journal of cell biology 21 36995368
2023 ETS2 promotes cardiomyocyte apoptosis and autophagy in heart failure by regulating lncRNA TUG1/miR-129-5p/ATG7 axis. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 21 37171262
2021 Prosurvival IL-7-Stimulated Weak Strength of mTORC1-S6K Controls T Cell Memory via Transcriptional FOXO1-TCF1-Id3 and Metabolic AMPKα1-ULK1-ATG7 Pathways. Journal of immunology (Baltimore, Md. : 1950) 21 34872976
2020 Anti-tumor immunity influences cancer cell reliance upon ATG7. Oncoimmunology 21 32923161
2019 Autophagy-related gene ATG7 participates in the asexual development, stress response and virulence of filamentous insect pathogenic fungus Beauveria bassiana. Current genetics 21 30879087
2023 Deacetylation of ATG7 drives the induction of macroautophagy and LC3-associated microautophagy. Autophagy 20 37999993
2021 TGF-β/YB-1/Atg7 axis promotes the proliferation of hepatic progenitor cells and liver fibrogenesis. Biochimica et biophysica acta. Molecular basis of disease 20 34662704
2023 Autophagy gene Atg7 regulates the development of radiation-induced skin injury and fibrosis of skin. Skin research and technology : official journal of International Society for Bioengineering and the Skin (ISBS) [and] International Society for Digital Imaging of Skin (ISDIS) [and] International Society for Skin Imaging (ISSI) 19 37357660
2022 MiR-146a-5p accelerates sepsis through dendritic cell activation and glycolysis via targeting ATG7. Journal of biochemical and molecular toxicology 19 35781746
2022 ATG7 is a haploinsufficient repressor of tumor progression and promoter of metastasis. Proceedings of the National Academy of Sciences of the United States of America 19 35867735
2019 MicroRNA-93 mediates cabergoline resistance by targeting ATG7 in prolactinoma. The Journal of endocrinology 18 30389900
2016 The putative autophagy regulator Atg7 affects the physiology and pathogenic mechanisms of Cryptococcus neoformans. Future microbiology 18 27750454
2024 CDK12 inhibition upregulates ATG7 triggering autophagy via AKT/FOXO3 pathway and enhances anti-PD-1 efficacy in colorectal cancer. Pharmacological research 17 38354870
2020 EVI1 induces autophagy to promote drug resistance via regulation of ATG7 expression in leukemia cells. Carcinogenesis 17 31593983
2018 Control of autophagosome size and number by Atg7. Biochemical and biophysical research communications 17 29906462
2020 Effect of miR-202-5p-mediated ATG7 on autophagy and apoptosis of degenerative nucleus pulposus cells. European review for medical and pharmacological sciences 16 32016953
2020 ATG7 promotes autophagy in sepsis‑induced acute kidney injury and is inhibited by miR‑526b. Molecular medicine reports 16 32323768
2018 Blocking LC3 lipidation and ATG12 conjugation reactions by ATG7 mutant protein containing C572S. Biochemical and biophysical research communications 16 30503495
2024 ISG15 Promotes Progression and Gemcitabine Resistance of Pancreatic Cancer Cells Through ATG7. International journal of biological sciences 15 38385083
2022 ATG7-mediated autophagy facilitates embryonic stem cell exit from naive pluripotency and marks commitment to differentiation. Autophagy 15 35311460
2020 miR-375 Inhibits Autophagy and Further Promotes Inflammation and Apoptosis of Acinar Cells by Targeting ATG7. Pancreas 15 32282768
2020 Proteaphagy in Mammalian Cells Can Function Independent of ATG5/ATG7. Molecular & cellular proteomics : MCP 15 32299840