Affinage

ATG7

Ubiquitin-like modifier-activating enzyme ATG7 · UniProt O95352

Length
703 aa
Mass
78.0 kDa
Annotated
2026-06-09
100 papers in source corpus 28 papers cited in narrative 28 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 7/7 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

ATG7 is an E1-like enzyme that drives canonical, LC3-lipidation-dependent macroautophagy by initiating two ubiquitin-like conjugation cascades, and it additionally functions as a multifunctional effector with autophagy-independent roles in cell cycle control, apoptosis, metabolism, and angiogenesis (PMID:23388412, PMID:22499945). Its catalytic Cys572 forms the thioester intermediate required to activate and transfer both LC3/Atg8 and ATG12, and a Cys572Ser substitution acts as a dominant-negative that traps stable LC3 and ATG12 intermediates and blocks autophagosome formation (PMID:30503495). ATG7 recruits the E2 enzymes ATG3 and ATG10 through noncanonical interfaces distinct from classical ubiquitin E1-E2 contacts, and structural work shows Atg8 engages the C-terminal α-helix and crossover loop to relieve autoinhibition during activation (PMID:23388412, PMID:29237558). This catalytic step distinguishes ATG7-dependent autophagy from alternative pathways: ATG5/ATG7-independent macroautophagy proceeds via Rab9-dependent membrane fusion without LC3 lipidation, and additional ATG7/ATG3-independent LC3 lipidation and autophagy programs operate in Drosophila midgut and elicited macrophages (PMID:19794493, PMID:23873149, PMID:33459130). ATG7 activity is gated by post-translational modification: acetylation is inhibitory and disrupts ATG3 binding, while K63-linked ubiquitination at K413 by TRIM7 and at K45 via the ATM-CHK2-TRIM32 axis, and S-nitrosylation at Cys402 by transnitrosylating Trx1, all stimulate its E1-like activity and autophagy (PMID:37999993, PMID:36576150, PMID:37943659, PMID:36480290). Independent of its enzymatic function, ATG7 binds p53 to control p21/CDKN1A transcription and starvation-induced cell cycle arrest, restrains caspase-9 apoptotic activity, binds PKM2 to suppress its Tyr105 phosphorylation and the Warburg effect, and in endothelial cells sequesters ZNF148 in the cytoplasm to regulate STAT1/HIF1A-dependent angiogenesis (PMID:22499945, PMID:24362031, PMID:29910687, PMID:36300763). Biallelic loss-of-function variants in human ATG7 cause a neurodevelopmental disorder with cerebellar and corpus callosum abnormalities, with patient cells showing diminished ATG7 protein and severely reduced autophagic flux (PMID:34161705).

Mechanistic history

Synthesis pass · year-by-year structured walk · 27 steps
  1. 2004 Medium

    Established ATG7 as a genetically essential effector of a non-apoptotic, autophagic cell death program, framing autophagy machinery as a determinant of cell fate beyond bulk degradation.

    Evidence Genetic loss-of-function of ATG7/beclin 1 with cell death readout downstream of caspase-8 inhibition

    PMID:15131264

    Open questions at the time
    • Did not define ATG7's enzymatic contribution to this death program
    • No molecular mechanism linking ATG7 to RIP/JNK signaling
  2. 2009 High

    Defined the boundary of ATG7 requirement by showing it is needed only for canonical LC3-lipidation autophagy, not for Rab9-dependent alternative macroautophagy.

    Evidence Reciprocal Atg5/Atg7 knockout mouse cells with EM and LC3 lipidation assays

    PMID:19794493

    Open questions at the time
    • Did not establish what triggers the alternative pathway in lieu of ATG7
    • Mechanism of Rab9-dependent membrane fusion unresolved
  3. 2012 High

    Revealed the first autophagy-independent function of ATG7: enzyme-activity-independent binding to p53 to control p21 transcription and starvation-induced cell cycle arrest.

    Evidence Co-IP, E1-mutant rescue, and Atg7-KO MEFs with Chk2-deletion epistasis

    PMID:22499945

    Open questions at the time
    • Structural basis of ATG7-p53 binding unknown
    • How ATG7 influences p53 target selectivity unresolved
  4. 2013 High

    Provided the structural mechanism for how ATG7 recruits its E2 partners ATG3 and ATG10 through noncanonical interfaces, explaining substrate-specific routing in the two conjugation systems.

    Evidence Crystal structures of Atg7-Atg3 and Atg7-Atg10 complexes with mechanistic analysis

    PMID:23388412

    Open questions at the time
    • Did not resolve the full activation transfer cycle in vivo
    • Regulation of E2 selection under different stimuli unaddressed
  5. 2013 Medium

    Extended ATG7's noncatalytic interaction network to apoptosis by demonstrating reciprocal cross-regulation with caspase-9.

    Evidence Reciprocal Co-IP with caspase catalytic mutants and LC3-II assays

    PMID:24362031

    Open questions at the time
    • Reciprocal Co-IP from a single lab without structural validation
    • Physiological context where this cross-talk dominates is undefined
  6. 2013 High

    Demonstrated in Drosophila that an autophagy program can run without ATG7/ATG3, instead requiring ubiquitin E1 (UBA1), reinforcing that ATG7 is specific to the ATG8 conjugation route.

    Evidence Atg7/Atg3 loss-of-function genetics in Drosophila midgut with Uba1 epistasis and EM

    PMID:23873149

    Open questions at the time
    • Conservation of this UBA1-driven program in mammals untested here
    • Membrane source for the ATG7-independent autophagy unknown
  7. 2014 Medium

    Identified acetylation as an inhibitory switch on ATG7 controlled by BAT3-modulated p300 localization, linking ATG7 activity to acetyltransferase compartmentalization.

    Evidence BAT3-KO MEFs, p300 localization, acetylation IP, cytosol-only BAT3 rescue

    PMID:24591579

    Open questions at the time
    • Specific acetylated residues not pinpointed here
    • Deacetylase responsible for reversal not identified
  8. 2017 High

    Resolved the Atg8-ATG7 recognition mode, showing Atg8 binds the C-terminal helix/crossover loop to relieve autoinhibition, refining the activation mechanism.

    Evidence Crystal structure of Atg8-ATG7 C-terminal domain with mutagenesis and activation assays

    PMID:29237558

    Open questions at the time
    • Did not capture the full thioester transfer step
    • Conformational dynamics during catalysis not measured
  9. 2018 Medium

    Connected ATG7 to cancer metabolism by showing it binds PKM2 and blocks its Tyr105 phosphorylation, suppressing the Warburg effect and EMT independently of autophagy.

    Evidence Co-IP, phosphorylation assays, Atg7 overexpression/knockdown, EMT assays

    PMID:29910687

    Open questions at the time
    • Structural basis of ATG7-PKM2 binding unknown
    • How ATG7 shields the FGFR1 target site mechanistically unresolved
  10. 2018 Medium

    Confirmed Cys572 as the catalytic thioester residue by showing C572S traps LC3 and ATG12 intermediates and acts as a dominant-negative.

    Evidence ATG7 C572S expression with LC3/ATG12 conjugation and autophagosome assays

    PMID:30503495

    Open questions at the time
    • Single-lab biochemistry without structural snapshot of the trapped intermediate
  11. 2018 High

    Linked posttranscriptional control of ATG7 (via CCR4-NOT deadenylation) to its p53-dependent cardiomyocyte death function, demonstrating in vivo that the ATG7-p53 axis drives pathology.

    Evidence Cnot conditional KO mice with Atg7 genetic ablation epistasis, deadenylation assays, Atg7-p53 Co-IP

    PMID:29438013

    Open questions at the time
    • Whether p53 modulation requires ATG7 catalytic activity not fully separated
    • Generality beyond cardiomyocytes untested
  12. 2018 Medium

    Extended ATG7's noncatalytic protein-binding repertoire to PKC-delta activation in renal tubular apoptosis during nephrotoxicity.

    Evidence Proximal-tubule Atg7 KO mice, Atg7-PKCδ Co-IP, PKCδ rescue

    PMID:30589566

    Open questions at the time
    • Single-lab Co-IP; direct binding interface undefined
    • Whether autophagy contributes in parallel not excluded
  13. 2019 Medium

    Showed that ATG7 engagement with LC3 is scaffolded by TP53INP2 in a trimeric LC3B-TP53INP2-ATG7 complex that promotes autophagosome formation.

    Evidence Reciprocal Co-IP, pulldown, LIR mutants, colocalization with autophagic markers

    PMID:30767704

    Open questions at the time
    • Structural arrangement of the trimer unknown
    • Whether TP53INP2 affects catalytic transfer or only proximity unresolved
  14. 2019 Low

    Implicated ATG7-dependent autophagy in bladder cancer invasion via HNRNPD degradation and ARHGDIB mRNA stabilization.

    Evidence ATG7 knockdown, HNRNPD-ARHGDIB interaction and degradation assays, invasion assays

    PMID:31016112

    Open questions at the time
    • Indirect multi-step mechanistic chain from single lab
    • Direct role of ATG7 enzymatic activity not isolated
  15. 2021 Medium

    Showed that ATG7 protein levels are tuned by m6A modification of its mRNA, linking RNA methylation to autophagy-dependent control of senescence in osteoarthritis.

    Evidence MeRIP, RIP, mRNA stability assays, METTL3 knockdown, flux assays

    PMID:34706873

    Open questions at the time
    • m6A reader mediating decay not defined here
    • Generality beyond synoviocytes untested
  16. 2021 Medium

    Demonstrated a mammalian exception in macrophages where LC3-PE conjugation occurs without ATG7/ATG3 but requires ATG5, challenging the universality of the canonical lipidation model.

    Evidence Atg7/Atg5 conditional KO and ATG3-KO macrophages with LC3-II immunoblot and flux assays

    PMID:33459130

    Open questions at the time
    • Alternative E1/E2 enzymes substituting for ATG7/ATG3 unidentified
    • Mechanism restricting this to the metabolic context unknown
  17. 2021 High

    Established ATG7 as indispensable for human degradative autophagy and as a Mendelian disease gene by linking biallelic loss-of-function to a neurodevelopmental disorder.

    Evidence Patient genetics, flux assays in patient fibroblasts/muscle, cross-species complementation with mutant ATG7

    PMID:34161705

    Open questions at the time
    • Cellular basis of cerebellar/corpus callosum pathology not fully defined
    • Contribution of noncatalytic ATG7 functions to the phenotype unresolved
  18. 2022 Medium

    Distinguished an autophagy-independent ATG7 role in tumor invasion mediated by succinate metabolism in a PDAC dosage model.

    Evidence Atg7 hemizygous PDAC mice, invasion assays, succinate metabolomics, ectopic ATG7 rescue without autophagy change

    PMID:35867735

    Open questions at the time
    • Molecular link between ATG7 and succinate accumulation undefined
    • Direct enzymatic partner in this metabolic role unknown
  19. 2022 Medium

    Identified K63-linked ubiquitination at K413 by TRIM7 as a stimulatory modification enhancing autophagy and antibacterial defense.

    Evidence Co-IP, K413 site-mutant ubiquitination assays, TRIM7-KO cells and mice

    PMID:36576150

    Open questions at the time
    • How K413 ubiquitination mechanistically activates E1 function unclear
    • Deubiquitinase reversing this mark unidentified
  20. 2022 Medium

    Linked ATG7-dependent autophagy to NANOG turnover via SQSTM1/p62 recognition of K63-ubiquitinated NANOG, controlling exit from naive pluripotency.

    Evidence ATG7-depleted ESCs, SQSTM1 Co-IP with ubiquitinated NANOG, RNA-seq/ATAC-seq, in vivo embryo analysis

    PMID:35311460

    Open questions at the time
    • Ubiquitin ligase tagging NANOG not identified
    • Nuclear-cytoplasmic routing of the degradation step unresolved
  21. 2023 Medium

    Mapped the ATM-CHK2-TRIM32 oxidative-stress axis to K45 K63-ubiquitination of ATG7, defining a damage-responsive activating cascade.

    Evidence Ordered phosphorylation/Co-IP assays, K45 site mutant, Chk2-/- stroke mouse model

    PMID:37943659

    Open questions at the time
    • Structural effect of K45 modification on E1 activity unknown
    • Interplay with K413 ubiquitination not addressed
  22. 2023 High

    Defined a redox activating mechanism whereby Trx1 transnitrosylates ATG7 at Cys402 to stimulate E1 activity and cardiac protection during ischemia.

    Evidence Atg7 C402S knock-in mice, in vitro transnitrosylation reconstitution, E1 activity and ischemia model

    PMID:36480290

    Open questions at the time
    • How Cys402 nitrosylation structurally enhances catalysis unresolved
    • Crosstalk with acetylation/ubiquitination switches untested
  23. 2023 Medium

    Confirmed acetylation as a direct inhibitory switch by showing it disrupts ATG3 binding and blocks LC3 lipidation, with deacetylation enabling macro- and microautophagy.

    Evidence Acetyl-site mutants, in vitro lipidation, ATG7-ATG3 Co-IP, cellular LAP/macroautophagy assays

    PMID:37999993

    Open questions at the time
    • Deacetylase identity not established here
    • Quantitative stoichiometry of acetylation in vivo unknown
  24. 2023 Medium

    Defined a noncatalytic endothelial function: cytoplasmic ATG7 sequesters ZNF148 to suppress STAT1-mediated repression of HIF1A and promote ischemic angiogenesis.

    Evidence EC-specific Atg7 KO mice, ChIP, Co-IP (ATG7-ZNF148, ZNF148-KPNB1), HIF1A and STAT1-inhibitor rescue

    PMID:36300763

    Open questions at the time
    • Direct ATG7-ZNF148 binding interface undefined
    • Relationship to other endothelial ATG7 functions unresolved
  25. 2023 Medium

    Extended endothelial ATG7 roles to blood-brain barrier integrity through PKA-CREB-dependent fibronectin production.

    Evidence EC-specific Atg7 KO mice, fibronectin/PKA/CREB assays, astrocyte endfeet imaging, BBB permeability

    PMID:36995368

    Open questions at the time
    • Whether this is autophagy-dependent not fully separated
    • Direct molecular target of ATG7 upstream of PKA unknown
  26. 2023 Medium

    Identified an autophagy-independent immunosuppressive role: ATG7 limits IRF3-driven interferon production via control of lncRNA GAPLINC during influenza infection.

    Evidence ATG7 conditional KO mice, transcriptome analysis, autophagy-inhibitor controls, GAPLINC manipulation

    PMID:38227600

    Open questions at the time
    • How ATG7 controls GAPLINC expression mechanistically undefined
    • Direct ATG7 binding partner in this pathway unidentified
  27. 2023 Low

    Proposed ISG15 binding stabilizes ATG7 to enhance autophagy and chemoresistance in pancreatic cancer.

    Evidence Co-IP, ATG7 stability assays, gemcitabine resistance models

    PMID:38385083

    Open questions at the time
    • Single Co-IP with indirect functional readout
    • Whether ISG15 covalently modifies or non-covalently binds ATG7 unresolved

Open questions

Synthesis pass · forward-looking unresolved questions
  • How ATG7's catalytic E1 activity, its layered post-translational switches (acetylation, K45/K413 ubiquitination, Cys402 nitrosylation), and its diverse noncatalytic protein-binding partners are integrated and prioritized in a given physiological context remains unresolved.
  • No unified structural model of how modifications converge on E1 activity
  • Hierarchy among autophagy-dependent vs independent functions in vivo undefined
  • Most noncatalytic partner interactions rest on single-lab Co-IP without structural validation

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140096 catalytic activity, acting on a protein 4 GO:0016874 ligase activity 2 GO:0060090 molecular adaptor activity 2 GO:0140110 transcription regulator activity 2 GO:0140657 ATP-dependent activity 2
Localization
GO:0005829 cytosol 2
Pathway
R-HSA-9612973 Autophagy 4 R-HSA-1643685 Disease 3 R-HSA-5357801 Programmed Cell Death 3 R-HSA-1430728 Metabolism 2 R-HSA-1640170 Cell Cycle 1
Partners
ATG10ATG3CASPASE-9LC3BP53PKM2TP53INP2ZNF148
Complex memberships
ATG12-ATG5 conjugation systemLC3B-TP53INP2-ATG7 trimeric complex

Evidence

Reading pass · 28 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2004 ATG7 and beclin 1 are required for autophagic cell death induced by activation of receptor-interacting protein and JNK kinases; this autophagic death pathway is induced by caspase-8 inhibition, placing ATG7 as an essential effector downstream of caspase-8 inhibition in a non-apoptotic death program. Genetic loss-of-function (ATG7/beclin 1 knockout/knockdown) with morphological and cell death phenotypic readout Science Medium 15131264
2009 ATG5 and ATG7 are dispensable for an alternative macroautophagy pathway in mouse cells; the ATG5/ATG7-independent alternative autophagy uses Rab9-dependent fusion of isolation membranes with trans-Golgi and late endosomal vesicles and does not involve LC3 lipidation, demonstrating that ATG7 is required only for the canonical LC3-lipidation-dependent autophagy pathway. Atg5/Atg7 knockout mouse cells, electron microscopy, LC3 lipidation assays, Rab9 dependency experiments Nature High 19794493
2012 ATG7, independent of its E1-like enzymatic activity, physically binds the tumor suppressor p53 and regulates transcription of the cell cycle inhibitor p21(CDKN1A) during nutrient starvation; Atg7-deficient MEFs fail to arrest the cell cycle under starvation, and prolonged Atg7 deficiency leads to increased DNA damage and p53-dependent apoptosis. Co-immunoprecipitation (Atg7-p53 interaction), E1-enzymatic-activity mutant rescue, Atg7 knockout mouse embryonic fibroblasts, p21 transcription assays, Chk2 deletion epistasis Science High 22499945
2013 ATG7 (E1) recruits E2 enzymes ATG3 and ATG10 through noncanonical mechanisms distinct from canonical ubiquitin E1-E2 interactions; structural studies revealed the basis for these E2 recruitment modes in the context of the two ubiquitin-like conjugation systems (Atg8 and Atg12) essential for autophagosome biogenesis. Crystal structures of Atg7-Atg3 and Atg7-Atg10 complexes, structural and mechanistic analysis Autophagy High 23388412
2013 Caspase-9 forms a direct protein complex with ATG7; ATG7 represses the apoptotic activity of caspase-9 through direct interaction (not via autophagic function), while caspase-9 (in a catalytic-activity-independent manner) enhances ATG7-mediated LC3-II formation, revealing reciprocal cross-regulation between autophagy and apoptosis. Co-immunoprecipitation, caspase catalytic mutants, ATG7 knockdown, LC3-II formation assays The Journal of Biological Chemistry Medium 24362031
2013 In Drosophila intestinal cells, ATG7 and ATG3 are dispensable for autophagy-mediated programmed reduction of cell size during midgut cell death, while UBA1 (the ubiquitin E1 enzyme) is required; this defines an ATG7/ATG3-independent autophagy program in which ubiquitin activation (not the ATG8 conjugation system) drives autophagy. Atg7 and Atg3 loss-of-function genetics in Drosophila intestine, epistasis with Uba1, electron microscopy Nature Cell Biology High 23873149
2014 BAT3 controls autophagy by modulating p300 intracellular localization: BAT3 limits p300-dependent acetylation of ATG7 (which inhibits autophagy when acetylated) while simultaneously promoting p300-dependent acetylation of p53 (which promotes autophagy via pro-autophagic target genes). Loss of BAT3 results in ATG7 hyperacetylation and abolished autophagy. BAT3 knockout mouse embryos and MEFs, p300 localization assays, acetylation immunoprecipitation, BAT3 cytosol-only mutant rescue Proceedings of the National Academy of Sciences Medium 24591579
2017 Crystal structure of Atg8 bound to the C-terminal domain of ATG7 revealed an unprecedented binding mode: Atg8 binds the C-terminal α-helix and crossover loop of ATG7 (not the central β-sheet or catalytic site as in previously reported structures), changing the autoinhibited crossover loop conformation; mutational analyses confirmed this multi-step recognition mechanism is important for the activation reaction. Crystal structure of Atg8–ATG7(C-terminal domain) complex, site-directed mutagenesis, activation assays Journal of Molecular Biology High 29237558
2018 ATG7 binds PKM2 and prevents its phosphorylation at Tyr-105 by FGFR1, thereby inhibiting the Warburg effect; Atg7 deficiency leads to hyperphosphorylation of PKM2, promoting the Warburg effect and epithelial-mesenchymal transition (EMT) independently of ATG7's autophagic function. Co-immunoprecipitation (ATG7-PKM2 interaction), phosphorylation assays, Atg7 overexpression/knockdown, EMT phenotypic assays International Journal of Biological Sciences Medium 29910687
2018 In Cnot3-deficient hearts, ATG7 is posttranscriptionally upregulated (Cnot3 binds and shortens the Atg7 mRNA poly(A) tail); upregulated ATG7 interacts with p53 and modulates p53 activity to induce expression of cell death-promoting genes in cardiomyocytes. Genetic ablation of Atg7 (but not Atg5) rescues cardiac function and increases survival of Cnot1/Cnot3 knockout mice. CCR4-NOT complex conditional KO mice, Atg7 genetic ablation epistasis, mRNA deadenylation assays, Atg7-p53 interaction, cardiac function assays Science Signaling High 29438013
2018 ATG7 C572S (serine substitution of the catalytic cysteine) forms stable intermediate complexes with LC3 and ATG12, thereby acting as a dominant-negative inhibitor that blocks both LC3-PE conjugation and ATG12-ATG5 conjugation and suppresses autophagosome formation; this confirms that Cys572 forms the catalytic thioester bond essential for ATG7 E1-like activity. ATG7 C572S mutant expression in TetOff cells, LC3/ATG12 conjugation assays, autophagosome formation assays Biochemical and Biophysical Research Communications Medium 30503495
2019 TP53INP2 forms a trimeric complex LC3B-TP53INP2-ATG7 in the cytoplasm; TP53INP2 promotes LC3B-ATG7 interaction by directly interacting with both LC3B (via its LIR motif) and ATG7, and loss of either TP53INP2-LC3 or TP53INP2-ATG7 interaction significantly reduces LC3B-ATG7 binding and autophagosome formation. Co-immunoprecipitation, pulldown, LIR mutants, BECN1/ATG5 deletion epistasis, colocalization with early autophagic markers Autophagy Medium 30767704
2021 In thioglycolate-elicited mouse peritoneal macrophages, ATG7 and ATG3 are dispensable for LC3-PE (LC3-II) conjugation, while ATG5 is required; this demonstrates that in this specific metabolic context, LC3 lipidation occurs through an ATG7/ATG3-independent mechanism, revealing a eukaryotic exception to the canonical yeast-based LC3 lipidation model. Atg7 and Atg5 conditional KO macrophages, ATG3 knockout, LC3-II immunoblot, bafilomycin A1 flux assays Autophagy Medium 33459130
2021 METTL3-mediated m6A modification of ATG7 mRNA decreases ATG7 RNA stability, reducing ATG7 protein expression; this impaired ATG7-dependent autophagy promotes GATA4 accumulation, leading to cellular senescence in fibroblast-like synoviocytes and OA progression. m6A methylated RNA immunoprecipitation, RNA immunoprecipitation, ATG7 mRNA stability assays, METTL3 siRNA knockdown, autophagic flux assays Annals of the Rheumatic Diseases Medium 34706873
2021 Biallelic loss-of-function variants in human ATG7 cause a neurodevelopmental disorder with cerebellar and corpus callosum abnormalities; patient fibroblasts show severely diminished ATG7 protein with markedly reduced autophagic flux; reintroduction of patient-derived mutant ATG7 into model systems failed to rescue LC3 lipidation, confirming ATG7 is indispensable for canonical degradative autophagy in humans. Patient genetics, autophagic flux assays in patient fibroblasts and skeletal muscle, long-lived protein degradation assays, yeast and MEF complementation with mutant ATG7 The New England Journal of Medicine High 34161705
2022 TRIM7/RNF90 (a RING-type E3 ubiquitin ligase) promotes K63-linked ubiquitination of ATG7 at K413, which enhances autophagosome accumulation during starvation, rapamycin stimulation, and L. monocytogenes infection; TRIM7 deficiency reduces autophagy and increases bacterial infection. Co-immunoprecipitation (TRIM7-ATG7 interaction), ubiquitination assays with K413 site mutant, TRIM7 KO cells and mice, autophagosome quantification Autophagy Medium 36576150
2023 Under oxidative stress, the ATM-CHK2-TRIM32 axis regulates ATG7 ubiquitination: ROS activate ATM (S1981 phosphorylation), which phosphorylates CHK2 (T68), which binds and phosphorylates TRIM32 (S55), which then mediates K63-linked ubiquitination of ATG7 at K45 to initiate autophagy; Chk2-/- mice show reduced TRIM32 phosphorylation, reduced ATG7 ubiquitination, and aggravated infarction after stroke. Phosphorylation assays, Co-IP of CHK2-TRIM32 and TRIM32-ATG7, K45 ubiquitination site-specific mutant, Chk2-/- mouse stroke model Cell Reports Medium 37943659
2023 Thioredoxin 1 (Trx1) transnitrosylates ATG7 at Cys402 during myocardial ischemia: ischemia-oxidized Trx1 (Cys32-Cys35 disulfide, S-nitrosylated at Cys73) undergoes thiol-disulfide exchange with ATG7 Cys545-Cys548, releasing NO from Trx1 Cys73 and transferring it to ATG7 Cys402; S-nitrosylation of ATG7 at Cys402 stimulates its E1-like enzyme activity, promoting autophagy and cardiac protection during ischemia. Atg7 C402S knock-in mice, in vitro thiol-disulfide exchange and transnitrosylation assays, E1-like activity measurement, ischemia model The Journal of Clinical Investigation High 36480290
2023 Acetylation of ATG7 disrupts its interaction with the E2-like enzyme ATG3, inhibiting LC3 lipidation in vitro and in vivo; in response to various stimuli, ATG7 undergoes deacetylation to induce macroautophagy and LC3-associated microautophagy, which are necessary for eliminating cytoplasmic DNA and degrading lysosome membrane proteins, respectively. ATG7 acetylation site mutants, in vitro LC3 lipidation assay, ATG7-ATG3 co-immunoprecipitation, cell-based macroautophagy and LAP assays Autophagy Medium 37999993
2023 Endothelial ATG7 promotes angiogenesis through an autophagy-independent mechanism: in the cytoplasm, ATG7 associates with transcription factor ZNF148/ZBP-89, preventing its nuclear translocation; loss of ATG7 increases ZNF148-KPNB1 interaction promoting ZNF148 nuclear import, which upregulates STAT1, which then binds the HIF1A promoter and suppresses HIF1A expression, impairing ischemia-induced angiogenesis. EC-specific Atg7 KO mice, ChIP (STAT1 on HIF1A promoter), Co-IP (ATG7-ZNF148, ZNF148-KPNB1), HIF1A overexpression rescue, STAT1 inhibitor rescue, femoral artery ligation model Autophagy Medium 36300763
2023 ATG7 suppresses IRF3-mediated interferon production in an autophagy-independent manner during influenza A virus infection by controlling expression of lncRNA GAPLINC; loss of ATG7 enhances type I and III interferon production, and the suppressive effect of ATG7 on IFN response is mediated through GAPLINC. ATG7 conditional KO mice, ATG7 overexpression/depletion in cells, transcriptome analysis, autophagy inhibitor controls, GAPLINC expression manipulation, IRF3 activation assays PLoS Pathogens Medium 38227600
2023 Endothelial ATG7 is required for fibronectin production in the blood-brain barrier basement membrane via regulation of PKA activity and phosphorylation of CREB; Atg7 endothelial-specific KO reduces fibronectin expression, causing astrocytic endfeet detachment from microvessels and BBB leakage. Atg7 endothelial-specific KO mice, fibronectin immunostaining and quantification, PKA activity assays, CREB phosphorylation, astrocyte endfeet imaging, BBB permeability assays The Journal of Cell Biology Medium 36995368
2022 ATG7 hemizygosity in a PDAC model (KrasG12D/+; Trp53R172H/+) enhances tumor initiation and progression without ablating autophagy, but fewer hemizygous mice develop metastases; ATG7 promotes tumor cell invasion through succinate metabolism (Atg7+/- tumors have lower succinate), and ectopic ATG7 expression in Atg7+/- cells restores invasion without affecting autophagic capacity, demonstrating an autophagy-independent role of ATG7 in invasion and metastasis. Atg7 hemizygous PDAC mouse model, invasion assays, metabolomics (succinate), ATG7 ectopic expression rescue, autophagy capacity assays Proceedings of the National Academy of Sciences Medium 35867735
2018 ATG7 mediates renal tubular cell apoptosis during vancomycin nephrotoxicity by binding to and activating PKC-δ; Atg7 conditional KO (proximal tubule-specific) ameliorates vancomycin-induced kidney injury and apoptosis, and this renoprotective effect is lost after injection of myc-tagged PKCδ. Proximal tubule-specific Atg7 KO mice, co-immunoprecipitation (Atg7-PKCδ), PKCδ inhibitor rescue, global gene expression analysis FASEB Journal Medium 30589566
2023 ISG15 binds to ATG7 protein, reducing its degradation and thereby enhancing ATG7-dependent autophagy in pancreatic cancer cells, promoting cancer progression and gemcitabine resistance. Co-immunoprecipitation (ISG15-ATG7), ATG7 protein stability assays, autophagy flux assays, in vitro and in vivo gemcitabine resistance models International Journal of Biological Sciences Low 38385083
2016 In brain microvascular endothelial cells, ATG7 knockdown reduces IL-6 expression through NF-κB-dependent transcriptional control; endothelial-specific Atg7 KO mice show decreased brain microvessel density, and exogenous IL-6 restores impaired angiogenesis caused by ATG7 knockdown, demonstrating that ATG7 promotes brain angiogenesis via NF-κB-dependent IL-6 production. Atg7 endothelial-specific KO mice, ATG7 knockdown in brain endothelial cells, IL-6 measurement, NF-κB reporter assay, IL-6 rescue experiment, microvessel density quantification International Journal of Molecular Sciences Medium 28467355
2019 ATG7 promotes bladder cancer invasion through an autophagy-mediated mechanism: ATG7-dependent autophagy causes degradation of HNRNPD protein, reducing HNRNPD interaction with ARHGDIB mRNA, which increases ARHGDIB mRNA stability and promotes invasion. ATG7 knockdown in human bladder cancer cells, HNRNPD-ARHGDIB mRNA interaction assays, ATG7-mediated HNRNPD protein degradation assays, invasion assays Advanced Science Low 31016112
2021 ATG7-mediated autophagy promotes degradation of NANOG in embryonic stem cells via SQSTM1/p62 acting as an autophagy receptor for K63-ubiquitinated NANOG; loss of ATG7 increases nuclear NANOG, prevents exit from naive pluripotency, and disrupts peri-implantation development. ATG7-depleted ESCs, SQSTM1/p62 nuclear localization and Co-IP with K63-ubiquitinated NANOG, RNA-seq, ATAC-seq, 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.) 1064 15131264
2009 Discovery of Atg5/Atg7-independent alternative macroautophagy. Nature 932 19794493
2011 The autophagy protein Atg7 is essential for hematopoietic stem cell maintenance. The Journal of experimental medicine 514 21339326
2019 m6A mRNA methylation controls autophagy and adipogenesis by targeting Atg5 and Atg7. Autophagy 321 31451060
2021 METTL3-mediated m6A modification of ATG7 regulates autophagy-GATA4 axis to promote cellular senescence and osteoarthritis progression. Annals of the rheumatic diseases 320 34706873
2012 Atg7 modulates p53 activity to regulate cell cycle and survival during metabolic stress. Science (New York, N.Y.) 283 22499945
2014 Atg7 is required for acrosome biogenesis during spermatogenesis in mice. Cell research 215 24853953
2015 Atg7 Overcomes Senescence and Promotes Growth of BrafV600E-Driven Melanoma. Cancer discovery 182 25673642
2021 Emerging roles of ATG7 in human health and disease. EMBO molecular medicine 161 34725936
2013 Uba1 functions in Atg7- and Atg3-independent autophagy. Nature cell biology 156 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) 145 28258192
2021 Developmental Consequences of Defective ATG7-Mediated Autophagy in Humans. The New England journal of medicine 142 34161705
2017 Molecular mechanisms and physiological roles of Atg5/Atg7-independent alternative autophagy. Proceedings of the Japan Academy. Series B, Physical and biological sciences 142 28603209
2016 Neuroprotection by selective neuronal deletion of Atg7 in neonatal brain injury. Autophagy 139 26727396
2019 ATG5 and ATG7 induced autophagy interplays with UPR via PERK signaling. Cell communication and signaling : CCS 136 31060556
2016 The long noncoding RNA HOTAIR activates autophagy by upregulating ATG3 and ATG7 in hepatocellular carcinoma. Molecular bioSystems 136 27301338
2012 Autophagy-related gene 7 (ATG7) and reactive oxygen species/extracellular signal-regulated kinase regulate tetrandrine-induced autophagy in human hepatocellular carcinoma. The Journal of biological chemistry 114 22927446
2016 Atg7 suppression enhances chemotherapeutic agent sensitivity and overcomes stroma-mediated chemoresistance in acute myeloid leukemia. Blood 112 27268264
2015 Atg7 in development and disease: panacea or Pandora's Box? Protein & cell 97 26404030
2017 Autophagy gene ATG7 regulates ultraviolet radiation-induced inflammation and skin tumorigenesis. Autophagy 95 28933598
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 90 27168493
2016 TRIM31 promotes Atg5/Atg7-independent autophagy in intestinal cells. Nature communications 89 27216961
2019 MiRNA-192-5p attenuates airway remodeling and autophagy in asthma by targeting MMP-16 and ATG7. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 85 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
2022 Autophagic Schwann cells promote perineural invasion mediated by the NGF/ATG7 paracrine pathway in pancreatic cancer. Journal of experimental & clinical cancer research : CR 78 35109895
2022 Rare ATG7 genetic variants predispose patients to severe fatty liver disease. Journal of hepatology 78 35405176
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
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 73 30224786
2020 Disruption of Atg7-dependent autophagy causes electromotility disturbances, outer hair cell loss, and deafness in mice. Cell death & disease 72 33099575
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 68 30767704
2019 ATG7 Promotes Bladder Cancer Invasion via Autophagy-Mediated Increased ARHGDIB mRNA Stability. Advanced science (Weinheim, Baden-Wurttemberg, Germany) 68 31016112
2023 ATG7 and ATG14 restrict cytosolic and phagosomal Mycobacterium tuberculosis replication in human macrophages. Nature microbiology 61 36959508
2018 The CCR4-NOT deadenylase complex controls Atg7-dependent cell death and heart function. Science signaling 60 29438013
2018 Long noncoding RNA HOTAIR regulates autophagy via the miR-20b-5p/ATG7 axis in hepatic ischemia/reperfusion injury. Gene 59 30367982
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 57 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 46 28778418
2019 LncRNA CCAT1 promotes autophagy via regulating ATG7 by sponging miR-181 in hepatocellular carcinoma. Journal of cellular biochemistry 40 31218739
2021 Silencing of ATG2 and ATG7 promotes programmed cell death in wheat via inhibition of autophagy under salt stress. Ecotoxicology and environmental safety 38 34509161
2020 RNA-binding protein HuR suppresses senescence through Atg7 mediated autophagy activation in diabetic intervertebral disc degeneration. Cell proliferation 38 33372336
2024 ANXA2 (annexin A2) is crucial to ATG7-mediated autophagy, leading to tumor aggressiveness in triple-negative breast cancer cells. Autophagy 37 38290972
2018 Atg7 inhibits Warburg effect by suppressing PKM2 phosphorylation resulting reduced epithelial-mesenchymal transition. International journal of biological sciences 35 29910687
2016 MAPK1/3 regulate hepatic lipid metabolism via ATG7-dependent autophagy. Autophagy 35 26760678
2013 Structures of Atg7-Atg3 and Atg7-Atg10 reveal noncanonical mechanisms of E2 recruitment by the autophagy E1. Autophagy 34 23388412
2017 Atg7 Activates an Autophagy-Essential Ubiquitin-like Protein Atg8 through Multi-Step Recognition. Journal of molecular biology 31 29237558
2015 Gene-gene interaction of ATG5, ATG7, BLK and BANK1 in systemic lupus erythematosus. International journal of rheumatic diseases 31 26420661
2021 ATG7 is dispensable for LC3-PE conjugation in thioglycolate-elicited mouse peritoneal macrophages. Autophagy 29 33459130
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
2024 Insights on E1-like enzyme ATG7: functional regulation and relationships with aging-related diseases. Communications biology 28 38553562
2022 Ablation of endothelial Atg7 inhibits ischemia-induced angiogenesis by upregulating Stat1 that suppresses Hif1a expression. Autophagy 28 36300763
2017 Atg7 Regulates Brain Angiogenesis via NF-κB-Dependent IL-6 Production. International journal of molecular sciences 28 28467355
2023 TRIM7/RNF90 promotes autophagy via regulation of ATG7 ubiquitination during L. monocytogenes infection. Autophagy 27 36576150
2023 ATM-CHK2-TRIM32 axis regulates ATG7 ubiquitination to initiate autophagy under oxidative stress. Cell reports 27 37943659
2022 Celastrol upregulated ATG7 triggers autophagy via targeting Nur77 in colorectal cancer. Phytomedicine : international journal of phytotherapy and phytopharmacology 26 35752079
2020 Discovery and optimization of pyrazolopyrimidine sulfamates as ATG7 inhibitors. Bioorganic & medicinal chemistry 26 32912429
2020 LncRNA DANCR promotes ATG7 expression to accelerate hepatocellular carcinoma cell proliferation and autophagy by sponging miR-222-3p. European review for medical and pharmacological sciences 26 32964966
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 Autophagy protein ATG7 is a critical regulator of endothelial cell inflammation and permeability. Scientific reports 24 32792588
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
2018 MiR-490-3p inhibits autophagy via targeting ATG7 in hepatocellular carcinoma. IUBMB life 23 29676845
2018 RNA-binding protein, human antigen R regulates hypoxia-induced autophagy by targeting ATG7/ATG16L1 expressions and autophagosome formation. Journal of cellular physiology 23 30317574
2017 Ultraviolet B radiation down-regulates ULK1 and ATG7 expression and impairs the autophagy response in human keratinocytes. Journal of photochemistry and photobiology. B, Biology 23 29154199
2023 Endothelial depletion of Atg7 triggers astrocyte-microvascular disassociation at blood-brain barrier. The Journal of cell biology 22 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 22 37171262
2022 MiR-146a-5p accelerates sepsis through dendritic cell activation and glycolysis via targeting ATG7. Journal of biochemical and molecular toxicology 22 35781746
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) 22 34872976
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
2020 Anti-tumor immunity influences cancer cell reliance upon ATG7. Oncoimmunology 22 32923161
2024 ATG7/GAPLINC/IRF3 axis plays a critical role in regulating pathogenesis of influenza A virus. PLoS pathogens 21 38227600
2023 Thioredoxin 1 promotes autophagy through transnitrosylation of Atg7 during myocardial ischemia. The Journal of clinical investigation 21 36480290
2023 Deacetylation of ATG7 drives the induction of macroautophagy and LC3-associated microautophagy. Autophagy 21 37999993
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 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) 20 37357660
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 20 35867735
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
2016 Bone morphogenetic protein-induced cell differentiation involves Atg7 and Wnt16 sequentially in human stem cell-derived osteoblastic cells. Experimental cell research 20 27397580
2023 Urinary stem cell-derived exocrine circRNA ATG7 regulates the SOCS1/STAT3 signaling pathway through miR-4500, inhibits M1 macrophage polarization, and alleviates the progression of diabetes nephropathy. International urology and nephrology 19 37815664
2022 ATG7-enhanced impaired autophagy exacerbates acute pancreatitis by promoting regulated necrosis via the miR-30b-5p/CAMKII pathway. Cell death & disease 18 35256590
2020 ATG7-dependent and independent autophagy determine the type of treatment in lung cancer. Pharmacological research 18 33276100
2019 MicroRNA-93 mediates cabergoline resistance by targeting ATG7 in prolactinoma. The Journal of endocrinology 18 30389900
2024 CDK12 inhibition upregulates ATG7 triggering autophagy via AKT/FOXO3 pathway and enhances anti-PD-1 efficacy in colorectal cancer. Pharmacological research 17 38354870
2018 Control of autophagosome size and number by Atg7. Biochemical and biophysical research communications 17 29906462
2021 Intracellular alpha-fetoprotein interferes with all-trans retinoic acid induced ATG7 expression and autophagy in hepatocellular carcinoma cells. Scientific reports 16 33495541
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
2022 Essential role for STAT3/FOXM1/ATG7 signaling-dependent autophagy in resistance to Icotinib. Journal of experimental & clinical cancer research : CR 15 35690866
2021 ATG7 safeguards human neural integrity. Autophagy 15 34313536
2020 Proteaphagy in Mammalian Cells Can Function Independent of ATG5/ATG7. Molecular & cellular proteomics : MCP 15 32299840

Missed literature

Know a paper Affinage missed for ATG7? Flag it for the maintainers and the community.

No submissions yet.