Affinage

MAP1LC3B

Microtubule-associated protein 1 light chain 3 beta · UniProt Q9GZQ8

Round 2 corrected
Length
125 aa
Mass
14.7 kDa
Annotated
2026-04-28
64 papers in source corpus 29 papers cited in narrative 29 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

MAP1LC3B is a central effector of macroautophagy that, upon C-terminal cleavage by Atg4B to expose Gly120, is conjugated to phosphatidylethanolamine via the Atg7 (E1-like) and Atg3 (E2-like) cascade, generating the membrane-bound LC3B-II form that specifically marks autophagosomal membranes (PMID:11060023, PMID:15355958). LC3B-II serves as a scaffold for selective autophagy by engaging LIR-motif-containing receptors—including p62/SQSTM1, NBR1, optineurin, Nix, PHB2, FAM134B, and FUNDC1—to direct degradation of ubiquitinated aggregates, mitochondria, ER, and intracellular bacteria (PMID:17580304, PMID:21617041, PMID:26040720, PMID:28017329). LC3B is also subject to multi-layered regulation: its transcription is induced by PERK–ATF4/CHOP signaling during ER stress, its translation is controlled by BAG3, its mRNA is modulated by m6A methylation, and the protein itself is negatively regulated by monoubiquitination mediated by HDAC6 and pVHL, and positively regulated by SIRT1-dependent deacetylation (PMID:20038797, PMID:18296641, PMID:40212005, PMID:30902965). Beyond canonical autophagy, LC3B mediates nuclear lamin B1 degradation during oncogene-induced senescence, functions as an RNA-binding protein directing maternal mRNA decay during the maternal-to-zygotic transition, and contributes to ferroptosis through autophagic ferritin turnover (PMID:26524528, PMID:41231099, PMID:31659150).

Mechanistic history

Synthesis pass · year-by-year structured walk · 14 steps
  1. 2000 High

    Identification of LC3-II as the first mammalian autophagosome-specific marker resolved a major gap in mammalian autophagy: no protein had been shown to specifically associate with autophagosomes, and this discovery established MAP1LC3B as the molecular handle for tracking autophagy.

    Evidence Subcellular fractionation, immunoelectron microscopy, and mutagenesis in mammalian cells

    PMID:11060023

    Open questions at the time
    • Enzymatic machinery for LC3 processing and lipidation was not yet identified
    • Functional role of LC3-II beyond membrane marking was unknown
  2. 2004 High

    Reconstitution of the LC3 conjugation cascade—Atg4B-mediated cleavage exposing Gly120 followed by Atg7/Atg3-dependent lipidation—established the complete enzymatic pathway generating LC3-II and revealed its mechanistic parallels to ubiquitin conjugation.

    Evidence In vitro cleavage and conjugation assays, G120A mutagenesis, RNAi validation

    PMID:15325588 PMID:15355958

    Open questions at the time
    • E3-like requirements for lipidation versus protein conjugation were unresolved
    • Structural basis for Atg4B recognition of LC3B was not determined
  3. 2007 High

    Discovery that p62/SQSTM1 binds LC3 through a defined 22-residue LIR motif to mediate degradation of ubiquitinated aggregates established the receptor-scaffold paradigm for selective autophagy, fundamentally reframing LC3-II from a passive marker to an active cargo-recruitment platform.

    Evidence Direct binding assays, LIR mapping, p62 knockdown with aggregate clearance readout

    PMID:17580304

    Open questions at the time
    • Whether other receptors use the same LIR-binding surface was unknown
    • Structural basis of the LIR–LC3 interaction was not resolved in this study
  4. 2008 High

    Demonstration that SIRT1 directly deacetylates LC3B in an NAD-dependent manner, and that Sirt1-deficient cells have impaired starvation-induced autophagy, revealed acetylation as a key post-translational switch controlling LC3B activity.

    Evidence In vitro deacetylation assay, Sirt1−/− MEFs, reconstitution with catalytic mutant

    PMID:18296641

    Open questions at the time
    • Specific acetylation sites on LC3B were not mapped
    • Identity of the acetyltransferase opposing SIRT1 was not established
  5. 2009 High

    Parallel identification of multiple LIR-containing selective autophagy receptors—NBR1 for aggregates, Nix/BNIP3L and FUNDC1 for mitochondria—demonstrated that LC3 functions as a universal docking platform for organelle-selective autophagy, greatly expanding its functional repertoire beyond aggrephagy.

    Evidence LIR mutagenesis, co-immunoprecipitation, reticulocyte maturation assay (Nix), mitophagy imaging (FUNDC1), p62-independent aggrephagy (NBR1)

    PMID:19250911 PMID:20010802 PMID:22267086

    Open questions at the time
    • Hierarchy or competition among receptors for LC3 binding was not addressed
    • How LC3 discriminates between GABARAP and LC3 subfamily members at receptor interfaces was unclear
  6. 2009 High

    Showing that PERK–ATF4/CHOP signaling transcriptionally induces MAP1LC3B during hypoxia and ER stress, and that PERK-deficient cells become depleted of LC3B protein, established the first transcriptional regulatory axis maintaining LC3B supply during prolonged autophagy.

    Evidence Transcriptional reporters, siRNA of PERK/ATF4/CHOP, xenograft immunostaining

    PMID:20038797

    Open questions at the time
    • Whether CHOP binds the MAP1LC3B promoter directly was not shown until later
    • Additional transcription factors regulating MAP1LC3B under other stresses were not explored
  7. 2010 High

    Systematic AP-MS interactome mapping of all six human ATG8 orthologues revealed that MAP1LC3B shares an extensive overlapping interaction network of ~67 partners, most engaging the conserved LIR-binding surface, clarifying functional redundancy and specificity among LC3/GABARAP family members.

    Evidence Affinity purification–mass spectrometry with RNAi-based functional validation

    PMID:20562859

    Open questions at the time
    • Quantitative binding affinities for individual LIR-containing partners were not determined
    • Context-dependent selectivity of LC3B versus other ATG8 family members remained unresolved
  8. 2011 High

    Optineurin was identified as a xenophagy receptor whose LC3-binding is regulated by TBK1 phosphorylation at Ser-177, establishing kinase-regulated receptor–LC3 affinity as a mechanism for stimulus-responsive selective autophagy of intracellular bacteria.

    Evidence In vitro TBK1 kinase assay, LIR mutagenesis, Salmonella clearance assay

    PMID:21617041

    Open questions at the time
    • Whether TBK1-mediated phosphorylation similarly regulates other LIR-containing receptors was not tested
  9. 2012 High

    Discovery that C18-ceramide directly binds LC3B-II and targets autophagolysosomes to mitochondria for lethal mitophagy revealed a lipid-signaling input to LC3B-dependent cargo selection, distinct from the protein LIR-based receptor paradigm.

    Evidence Molecular modeling, ceramide-binding-deficient LC3B mutant, xenograft tumor model

    PMID:22922758

    Open questions at the time
    • Crystal structure of ceramide–LC3B complex was not solved
    • Generalizability of lipid-directed LC3B targeting beyond ceramide was not explored
  10. 2015 High

    Two landmark studies expanded LC3B biology beyond cytoplasmic autophagy: LC3B mediates nuclear lamin B1 degradation during oncogene-induced senescence and serves as receptor for FAM134B-dependent ER-phagy, demonstrating that LC3B functions as a versatile degradation scaffold across multiple organellar compartments.

    Evidence Nuclear fractionation with RAS-induced senescence model (lamin B1); Fam134b knockout mice and LIR mutagenesis (ER-phagy)

    PMID:26040720 PMID:26524528

    Open questions at the time
    • Mechanism of LC3B nuclear export during senescence was not fully elucidated
    • Whether other nuclear substrates are degraded via LC3B-dependent nucleophagy was unknown
  11. 2016 High

    PHB2 was identified as the first inner mitochondrial membrane LC3 receptor, whose LIR becomes accessible only after outer membrane rupture, and BAG3 was shown to regulate LC3B protein levels translationally, revealing new layers of LC3B regulation at both the protein-level and receptor-access level.

    Evidence PHB2 LIR mutagenesis, Parkin-induced mitophagy assay, C. elegans paternal mitochondria clearance; BAG3 knockdown with polysome profiling

    PMID:26654586 PMID:28017329

    Open questions at the time
    • Protease(s) responsible for outer membrane rupture exposing PHB2 LIR were not identified
    • Mechanism by which BAG3 controls LC3B translation was not determined
  12. 2019 Medium

    Three studies collectively revealed LC3B as a node integrating post-translational inhibition (pVHL-mediated ubiquitination), iron-dependent cell death (ferroptosis via autophagic ferritin degradation), and tissue protection (LC3B−/− mice show increased lung fibrosis), broadening the physiological consequences of LC3B loss beyond autophagy per se.

    Evidence pVHL LIR mutagenesis with ubiquitination assays; LC3B−/− cell ferroptosis assays; bleomycin lung injury model in LC3B−/− mice

    PMID:30902965 PMID:31431059 PMID:31659150

    Open questions at the time
    • Whether pVHL-mediated LC3B ubiquitination occurs on specific lysine residues was not mapped
    • The cathepsin A–LC3B interaction lacks structural characterization
    • Relative contribution of LC3B versus other ATG8 family members to ferroptosis is unclear
  13. 2024 Medium

    m6A methylation of Map1lc3b mRNA by METTL3 was identified as a post-transcriptional regulatory mechanism that suppresses autophagy in Leydig cells, with the eraser ALKBH5 counteracting this effect, establishing epitranscriptomic control of LC3B expression.

    Evidence MeRIP-seq, METTL3/ALKBH5 manipulation, autophagy flux assays in BPA-exposed models

    PMID:39662354

    Open questions at the time
    • Specific m6A sites on MAP1LC3B mRNA were not mapped at single-nucleotide resolution
    • Whether m6A regulation of LC3B occurs in non-toxicological contexts is unknown
  14. 2025 Medium

    Two recent discoveries extended LC3B function in unexpected directions: HDAC6 mediates inhibitory monoubiquitination of LC3B contributing to cardiac hypertrophy, and LC3B was shown to bind maternal mRNAs as an RNA-binding protein, directing their degradation during the maternal-to-zygotic transition faster than canonical deadenylation pathways.

    Evidence HDAC6 co-IP and ubiquitination assays with isoproterenol cardiac hypertrophy model; RIP-seq, CUT&Tag, and LC3B knockdown in early embryos

    PMID:40212005 PMID:41231099

    Open questions at the time
    • Ubiquitination site(s) on LC3B targeted by HDAC6 are not identified
    • RNA-binding domain or motif on LC3B has not been structurally defined
    • Whether the RNA-binding function is conserved beyond mouse embryos is untested

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key unresolved questions include the structural basis of LC3B's RNA-binding activity, how LC3B discriminates among its many LIR-containing receptors in a context-dependent manner, the full scope and functional significance of protein ATG8ylation versus lipidation, and whether LC3B's non-autophagic functions (senescence, maternal mRNA decay, caspase-8 activation) share a common mechanistic principle.
  • No structural model of LC3B bound to RNA exists
  • Context-dependent receptor selectivity mechanism is unknown
  • Functional significance of protein ATG8ylation in vivo is uncharacterized

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0060090 molecular adaptor activity 5 GO:0031386 protein tag activity 4 GO:0008289 lipid binding 3 GO:0003723 RNA binding 1
Localization
GO:0031410 cytoplasmic vesicle 3 GO:0005829 cytosol 2 GO:0005634 nucleus 1 GO:0005886 plasma membrane 1
Pathway
R-HSA-9612973 Autophagy 11 R-HSA-392499 Metabolism of proteins 3 R-HSA-168256 Immune System 2 R-HSA-5357801 Programmed Cell Death 2 R-HSA-8953854 Metabolism of RNA 2 R-HSA-8953897 Cellular responses to stimuli 2
Partners
ATG3ATG4BATG7LMNB1OPTNPHB2SIRT1SQSTM1

Evidence

Reading pass · 29 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2000 LC3/MAP1LC3B, a mammalian homologue of yeast Apg8p, is post-translationally processed into two forms: LC3-I (cytosolic) and LC3-II (membrane-bound). LC3-II specifically associates with autophagosome membranes, and its amount correlates with the extent of autophagosome formation, establishing LC3-II as the first mammalian protein identified that specifically marks autophagosomal membranes. Subcellular fractionation, immunoelectron microscopy, mutational analysis, Western blotting The EMBO journal High 11060023
2003 MAP1LC3B undergoes a distinct post-translational modification compared to its paralogs MAP1LC3A and MAP1LC3C: rather than C-terminal proteolytic cleavage after a conserved Gly residue, MAP1LC3B modification involves Lys-122 as the essential site. All three isoforms associate with membranes in the autophagic pathway but show distinct expression patterns in human tissues. Cell fractionation, immunofluorescence, sequence analysis, site-directed mutagenesis The Journal of biological chemistry High 12740394
2004 The C-terminus of MAP1LC3B is cleaved by human Atg4B to expose Gly120, which is essential for subsequent ubiquitylation-like reactions: conjugation to phospholipid via Atg7 (E1-like) and Atg3 (E2-like), forming LC3B-II that partitions into the 100,000×g pellet (membrane fraction). G120A mutation abolishes both cleavage and conjugation. In vitro cleavage assay, in vitro conjugation assay, site-directed mutagenesis (G120A), RNA interference, subcellular fractionation The Journal of biological chemistry High 15355958
2004 MAP1LC3B lipidation (LC3-modification) requires two sequential ubiquitylation-like reactions: Atg7 (E1-like enzyme) activates LC3, which is then transferred to Atg3 (E2-like enzyme) before conjugation to phosphatidylethanolamine. Delipidation of LC3-II is mediated by hAtg4B. This LC3 conjugation cycle is functionally distinct from but interlinked with Atg12-conjugation. Biochemical conjugation assays, enzyme characterization, review synthesis of original experimental data The international journal of biochemistry & cell biology High 15325588
2007 p62/SQSTM1 directly binds LC3B (and LC3A) via a conserved 22-residue LC3-interacting region (LIR). This interaction is required for autophagic degradation of p62-positive ubiquitinated protein aggregates, and p62 is required for formation of polyubiquitin-containing inclusion bodies. Direct binding assays, co-immunoprecipitation, fluorescent reporter (tandem mCherry-GFP tag), siRNA knockdown, live-cell imaging The Journal of biological chemistry High 17580304
2008 SIRT1 forms a molecular complex with MAP1LC3B/Atg8 (along with Atg5 and Atg7) and can directly deacetylate these autophagy components in an NAD-dependent manner in vitro. Sirt1-deficient cells show elevated acetylation of autophagy proteins and fail to fully activate autophagy under starvation. Co-immunoprecipitation, in vitro deacetylation assay, Sirt1-/- mouse embryonic fibroblasts, reconstitution with wild-type vs. deacetylase-inactive mutant Proceedings of the National Academy of Sciences of the United States of America High 18296641
2009 FUNDC1, a mitochondrial outer-membrane protein, acts as a hypoxia-induced mitophagy receptor by directly interacting with LC3 through a canonical LC3-binding motif (Y18xxL21). Hypoxia induces dephosphorylation of FUNDC1, enhancing its interaction with LC3 and triggering selective mitophagy. Mutation of the LC3-interaction region abolishes mitophagy. Co-immunoprecipitation, mutagenesis of LIR motif, FUNDC1 knockdown/rescue, live-cell imaging of mitophagy Nature cell biology High 22267086
2009 Nix (BNIP3L), a mitochondrial protein, acts as a selective autophagy receptor by binding to LC3/GABARAP proteins via an N-terminal LC3-interacting region (LIR), and this interaction recruits GABARAP-L1 to damaged mitochondria. Ablation of the Nix:LC3/GABARAP interaction retards mitochondrial clearance in maturing murine reticulocytes. Co-immunoprecipitation, LIR mutagenesis, reticulocyte maturation assay (in vivo), live-cell imaging EMBO reports High 20010802
2009 LC3/Atg8 knockdown (RNAi) in PINK1-deficient neuronal cells decreases mitochondrial fragmentation, indicating that the autophagy machinery including LC3 actively participates in morphologic remodeling of mitochondria for clearance (mitophagy), independently of effects on oxidative stress. RNAi knockdown of LC3/Atg7, live-cell imaging of mitochondrial morphology and autophagy, PINK1 stable knockdown cell lines The Journal of biological chemistry Medium 19279012
2009 NBR1 is an autophagy receptor containing an LC3-interacting region (LIR) and ubiquitin-binding domain; NBR1 is recruited to ubiquitin-positive protein aggregates and degraded by autophagy in an LC3-family-modifier-dependent manner. NBR1 and p62 can function independently as selective autophagy receptors. Co-immunoprecipitation, LIR mutagenesis, autophagy flux assays, p62-deficient cell lines Molecular cell High 19250911
2009 Transcription of MAP1LC3B (and ATG5) is transcriptionally induced under hypoxia through the UPR transcription factors ATF4 and CHOP, downstream of PERK (EIF2AK3). This transcriptional upregulation replenishes MAP1LC3B protein consumed during extensive autophagy; PERK-deficient cells fail to induce MAP1LC3B transcription and become depleted of MAP1LC3B protein during hypoxia. Transcriptional reporter assays, siRNA knockdown of PERK/ATF4/CHOP, Western blotting, xenograft tumor models with immunostaining The Journal of clinical investigation High 20038797
2010 Proteomic mapping of the human autophagy interaction network revealed that the six ATG8 orthologues (including MAP1LC3B) interact with a cohort of 67 proteins, with extensive binding-partner overlap among family members, frequently mediated by a conserved surface on ATG8 proteins that engages LC3-interacting regions (LIRs) in partner proteins. Affinity purification–mass spectrometry (AP-MS) interactome mapping, RNAi validation of autophagosome number/flux effects Nature High 20562859
2011 Optineurin serves as a selective autophagy receptor linking ubiquitin-coated Salmonella to LC3-decorated autophagosomal membranes. TBK1 phosphorylates optineurin on Ser-177, enhancing its LC3-binding affinity and autophagic clearance of bacteria. LC3-binding-deficient optineurin mutants impair Salmonella autophagy. Phosphorylation mapping, in vitro kinase assay, LIR mutagenesis, LC3-binding affinity assays, intracellular bacterial proliferation assays, siRNA knockdown Science High 21617041
2012 C18-ceramide directly binds LC3B-II on autophagolysosomes and targets them to mitochondria via Drp1-dependent fission, leading to lethal mitophagy. Expression of a ceramide-binding-deficient LC3B mutant (predicted by molecular modeling) prevents CerS1-mediated mitochondrial targeting. Stable LC3B knockdown blocks CerS1/ceramide-dependent lethal mitophagy and tumor suppression in vivo. LC3B lipidation assays, molecular modeling of ceramide-LC3B interaction, mutagenesis, live-cell imaging of autophagolysosome trafficking, LC3B stable knockdown, in vivo xenograft tumor model Nature chemical biology High 22922758
2014 HCV core protein activates autophagy through EIF2AK3 and ATF6 UPR pathways: ATF4 (downstream of EIF2AK3) upregulates ATG12, while DDIT3/CHOP directly binds the MAP1LC3B promoter (−253 to −99 region) to upregulate LC3B transcription. The ERN1-XBP1 pathway was not involved. Promoter-binding assays (ChIP/EMSA implied), transcriptional reporter assays, siRNA knockdown of UPR components, Western blotting Autophagy Medium 24589849
2015 LC3/Atg8 (MAP1LC3B) is present in the nucleus and directly interacts with lamin B1 (a nuclear lamina protein), mediating its selective autophagic degradation upon oncogenic RAS activation. LC3-lamin B1 interaction does not regulate lamin B1 during starvation but specifically mediates nucleus-to-cytoplasm transport of lamin B1 for lysosomal degradation, which is required for oncogene-induced senescence. Co-immunoprecipitation, nuclear fractionation, live-cell imaging, RAS overexpression model, inhibition of autophagy/LC3-lamin B1 interaction Nature High 26524528
2015 FAM134B, an ER-resident reticulon protein, binds LC3 and GABARAP (including MAP1LC3B) to function as a receptor for selective ER autophagy (ER-phagy). FAM134B LIR-mediated interaction with LC3 is required for ER degradation; disease-causing FAM134B mutants cannot act as ER-phagy receptors. Co-immunoprecipitation, LIR mutagenesis, ER morphology analysis, Fam134b knockout mice, patient mutation analysis Nature High 26040720
2015 LC3B deficiency in Map1-LC3b knockout mice leads to increased IL-17a-dependent lung immunopathology during RSV infection. LC3b-deficient dendritic cells fail to upregulate autophagosome formation and instead secrete IL-1β and IL-6, promoting Th17 responses. ER stress sensor IRE1 in airway epithelial cells drives IL-1β production in the absence of LC3b-mediated autophagy. LC3b-/- knockout mice, bone marrow chimeras, IRE1 inhibition in primary airway epithelial cells, IL-1 receptor blockade in vivo Mucosal immunology Medium 25669150
2016 BAG3 regulates MAP1LC3B protein levels through a translational (not transcriptional) mechanism: BAG3 knockdown reduces total cellular LC3B protein without affecting LC3B mRNA levels or the LC3B lipidation process itself. This effect is specific to LC3B among ATG proteins tested. BAG3 siRNA knockdown, Western blotting, RT-qPCR, polysome profiling (translational assessment), nutrient deprivation and proteasome inhibition assays Autophagy Medium 26654586
2016 Prohibitin 2 (PHB2), an inner mitochondrial membrane protein, functions as a mitophagy receptor by binding LC3 through an LIR domain upon mitochondrial depolarization and proteasome-dependent outer membrane rupture. PHB2 is required for Parkin-induced mitophagy in mammalian cells and for paternal mitochondria clearance after fertilization in C. elegans. Co-immunoprecipitation, LIR mutagenesis, PHB2 knockdown/rescue, proteasome inhibition, C. elegans fertilization assay Cell High 28017329
2019 pVHL (von Hippel-Lindau protein) contains an LIR motif within its beta domain that interacts with MAP1LC3B and ubiquitinates it, thereby inhibiting LC3B-mediated autophagy. A VHL mutant (L101A) cannot interact with MAP1LC3B and fails to induce ubiquitination of LC3B. MAP1LC3B ubiquitination by pVHL is implicated in autophagy-induced cell death regulation in renal cell carcinoma. Co-immunoprecipitation, ubiquitination assays, LIR mutagenesis (L101A), VHL-deficient and VHL-expressing cell lines, autophagy flux assays Cell death & disease Medium 30902965
2019 In LC3B-/- cells (autophagy-deficient), erastin-induced autophagy that normally promotes ferroptosis by degrading ferritin (increasing intracellular iron) and inducing transferrin receptor 1 expression is abolished, resulting in iron depletion, reduced lipid peroxidation, and cell survival. This establishes LC3B-dependent autophagy as a key mediator of ferroptosis through regulation of iron homeostasis. LC3B-/- knockout cells, BECN1+/- cells, ferritin degradation assays, lipid peroxidation measurement, erastin-induced ferroptosis assays Cell death & disease High 31659150
2019 LC3B-/- mice show increased susceptibility to bleomycin-induced lung injury and fibrosis. Cathepsin A was identified as a novel LC3B binding partner; its overexpression drives alveolar epithelial cell apoptosis and its levels are increased in aged LC3B-/- mice and IPF patient lungs. LC3B-mediated autophagy protects alveolar epithelial cells from apoptosis. LC3B-/- knockout mice, bleomycin lung injury model, LC3B overexpression/knockdown in vitro, co-immunoprecipitation (cathepsin A), electron microscopy, proteasomal activity assays FASEB journal Medium 31431059
2020 MAP1LC3B has a non-autophagic function upstream of procaspase-8 cleavage in ER stress-induced apoptosis triggered by thapsigargin. Optimal cytotoxicity by thapsigargin requires MAP1LC3B protein in a manner independent of its autophagy function. ATF4 and CHOP independently regulate MAP1LC3B protein upregulation and death receptor 5 expression, acting in parallel rather than as a linear pathway. RNAi knockdown of MAP1LC3B and ATG proteins, caspase-8 cleavage assays, cell death measurement by fluorescence imaging/propidium iodide, Western blotting, real-time RT-PCR Cell communication and signaling : CCS Medium 31987044
2022 SQSTM1 (p62) and its MAP1LC3B-binding domain (LIR), when ectopically expressed at the mitochondrial outer membrane, directly induce selective mitophagy ('forced mitophagy'), degrading approximately half of mitochondria and their DNA in HeLa cells and mouse embryos without affecting mitochondrial membrane potential or embryo development. This forced mitophagy can reduce mitochondrial carryover in mitochondrial replacement therapy from ~4% to ~0.09%. Ectopic targeting constructs, mitochondrial DNA quantification, MMP assays, ROS measurement, mouse embryo development assays, human tri-pronuclear embryo experiments Autophagy Medium 35574946
2024 m6A RNA methylation by METTL3 specifically targets Map1lc3b mRNA in Leydig cells during BPA exposure, suppressing autophagy. The m6A eraser ALKBH5 counteracts this effect. Manipulating METTL3/ALKBH5 to reduce m6A methylation of Map1lc3b mRNA alleviates BPA-induced autophagic suppression and Leydig cell damage. MeRIP-seq, RNA-seq integration, METTL3/ALKBH5 manipulation (overexpression/knockdown), autophagy flux assays, in vivo and in vitro BPA exposure models Journal of hazardous materials Medium 39662354
2025 HDAC6 interacts with MAP1LC3B and mediates its monoubiquitination, reducing MAP1LC3B protein levels and impairing autophagy. In isoproterenol-induced cardiac hypertrophy, increased HDAC6 promotes hypertrophic responses by negatively regulating autophagy through MAP1LC3B ubiquitination. HDAC6 inhibition in vivo restores MAP1LC3B expression and attenuates hypertrophy. Co-immunoprecipitation, ubiquitination assays, HDAC6 overexpression/inhibition, in vivo ISO-induced cardiac hypertrophy mouse model, Western blotting The Journal of pathology Medium 40212005
2025 MAP1LC3B/LC3B functions as an RNA-binding protein during the maternal-to-zygotic transition, directly binding maternal mRNAs (identified by RIP-seq) and mediating their degradation with faster kinetics than the classical BTG4-CCR4-NOT pathway. LC3B knockdown or autophagy inhibition delays maternal mRNA clearance, impairs zygotic genome activation, and causes developmental arrest. Maternal Suv39h2 is a key LC3B-target transcript whose persistence correlates with developmental failure. RIP-seq, RNA-seq, CUT&Tag in early embryos, LC3B knockdown, autophagy inhibition, developmental arrest phenotyping Autophagy Medium 41231099
2024 Protein ATG8ylation (covalent attachment of MAP1LC3B to other cellular proteins) requires ATG7 (E1-like) and ATG3 (E2-like) in common with lipid ATG8ylation, but unlike lipidation, is independent of the E3-like ATG12-ATG5-ATG16L1 complex; ATG5 knockout cells can still form ATG8ylated protein conjugates. ATG7 itself is identified as a target of ATG8ylation. CRISPR/Cas9 knockout cell lines (ATG5 KO, ATG7 KO, ATG3 KO), deconjugation-resistant MAP1LC3B (Q116P G120) mutant, immunoprecipitation of protein-LC3B conjugates, Western blotting bioRxivpreprint Medium bio_10.1101_2024.07.03.601942

Source papers

Stage 0 corpus · 64 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2000 LC3, a mammalian homologue of yeast Apg8p, is localized in autophagosome membranes after processing. The EMBO journal 5854 11060023
2007 p62/SQSTM1 binds directly to Atg8/LC3 to facilitate degradation of ubiquitinated protein aggregates by autophagy. The Journal of biological chemistry 3823 17580304
2005 Towards a proteome-scale map of the human protein-protein interaction network. Nature 2090 16189514
2007 Homeostatic levels of p62 control cytoplasmic inclusion body formation in autophagy-deficient mice. Cell 1827 18083104
2005 A human protein-protein interaction network: a resource for annotating the proteome. Cell 1704 16169070
2002 Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences. Proceedings of the National Academy of Sciences of the United States of America 1479 12477932
2012 Mitochondrial outer-membrane protein FUNDC1 mediates hypoxia-induced mitophagy in mammalian cells. Nature cell biology 1380 22267086
2010 Network organization of the human autophagy system. Nature 1286 20562859
2008 A role for the NAD-dependent deacetylase Sirt1 in the regulation of autophagy. Proceedings of the National Academy of Sciences of the United States of America 1238 18296641
2004 LC3 conjugation system in mammalian autophagy. The international journal of biochemistry & cell biology 1224 15325588
2011 Phosphorylation of the autophagy receptor optineurin restricts Salmonella growth. Science (New York, N.Y.) 1074 21617041
2009 Nix is a selective autophagy receptor for mitochondrial clearance. EMBO reports 1062 20010802
2014 A proteome-scale map of the human interactome network. Cell 977 25416956
2009 A role for NBR1 in autophagosomal degradation of ubiquitinated substrates. Molecular cell 930 19250911
2020 A reference map of the human binary protein interactome. Nature 849 32296183
2012 A mega-analysis of genome-wide association studies for major depressive disorder. Molecular psychiatry 846 22472876
2000 DNA cloning using in vitro site-specific recombination. Genome research 815 11076863
2009 Loss of PINK1 function promotes mitophagy through effects on oxidative stress and mitochondrial fission. The Journal of biological chemistry 809 19279012
2015 Regulation of endoplasmic reticulum turnover by selective autophagy. Nature 772 26040720
2019 ROS-mediated autophagy increases intracellular iron levels and ferroptosis by ferritin and transferrin receptor regulation. Cell death & disease 763 31659150
2003 Complete sequencing and characterization of 21,243 full-length human cDNAs. Nature genetics 754 14702039
2016 Prohibitin 2 Is an Inner Mitochondrial Membrane Mitophagy Receptor. Cell 697 28017329
2009 The unfolded protein response protects human tumor cells during hypoxia through regulation of the autophagy genes MAP1LC3B and ATG5. The Journal of clinical investigation 678 20038797
2011 Phylogenetic-based propagation of functional annotations within the Gene Ontology consortium. Briefings in bioinformatics 656 21873635
2015 Autophagy mediates degradation of nuclear lamina. Nature 517 26524528
2010 FYCO1 is a Rab7 effector that binds to LC3 and PI3P to mediate microtubule plus end-directed vesicle transport. The Journal of cell biology 514 20100911
2014 ULK1 translocates to mitochondria and phosphorylates FUNDC1 to regulate mitophagy. EMBO reports 475 24671035
2012 Ceramide targets autophagosomes to mitochondria and induces lethal mitophagy. Nature chemical biology 453 22922758
2004 The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome research 438 15489334
2015 A Dynamic Protein Interaction Landscape of the Human Centrosome-Cilium Interface. Cell 433 26638075
2022 OpenCell: Endogenous tagging for the cartography of human cellular organization. Science (New York, N.Y.) 432 35271311
2003 Post-translational modifications of three members of the human MAP1LC3 family and detection of a novel type of modification for MAP1LC3B. The Journal of biological chemistry 247 12740394
2004 Human light chain 3/MAP1LC3B is cleaved at its carboxyl-terminal Met121 to expose Gly120 for lipidation and targeting to autophagosomal membranes. The Journal of biological chemistry 217 15355958
2014 Hepatitis C virus core protein activates autophagy through EIF2AK3 and ATF6 UPR pathway-mediated MAP1LC3B and ATG12 expression. Autophagy 127 24589849
2020 Cell death induced by the ER stressor thapsigargin involves death receptor 5, a non-autophagic function of MAP1LC3B, and distinct contributions from unfolded protein response components. Cell communication and signaling : CCS 100 31987044
2015 Deficiency of autophagy protein Map1-LC3b mediates IL-17-dependent lung pathology during respiratory viral infection via ER stress-associated IL-1. Mucosal immunology 73 25669150
2013 Progesterone receptor membrane component 1/Sigma-2 receptor associates with MAP1LC3B and promotes autophagy. Autophagy 64 24113030
2016 BAG3 regulates total MAP1LC3B protein levels through a translational but not transcriptional mechanism. Autophagy 29 26654586
2015 Monitoring Autophagic Flux by Using Lysosomal Inhibitors and Western Blotting of Endogenous MAP1LC3B. Cold Spring Harbor protocols 28 26240408
2019 Ubiquitination of MAP1LC3B by pVHL is associated with autophagy and cell death in renal cell carcinoma. Cell death & disease 27 30902965
2024 Mir221- and Mir222-enriched adsc-exosomes mitigate PM exposure-exacerbated cardiac ischemia-reperfusion injury through the modulation of the BNIP3-MAP1LC3B-BBC3/PUMA pathway. Autophagy 26 39245438
2015 MAP1LC3B overexpression protects against Hermansky-Pudlak syndrome type-1-induced defective autophagy in vitro. American journal of physiology. Lung cellular and molecular physiology 25 26719147
2009 Immunohistochemical expression of MAP1LC3A and MAP1LC3B protein in breast carcinoma tissues. Journal of clinical laboratory analysis 23 19623642
2018 A Rare Variant (rs933717) at FBXO31-MAP1LC3B in Chinese Is Associated With Systemic Lupus Erythematosus. Arthritis & rheumatology (Hoboken, N.J.) 21 29044928
2018 CRISPR/Cas9 Mediated GFP Knock-in at the MAP1LC3B Locus in 293FT Cells Is Better for Bona Fide Monitoring Cellular Autophagy. Biotechnology journal 20 29673078
2019 Susceptibility of microtubule-associated protein 1 light chain 3β (MAP1LC3B/LC3B) knockout mice to lung injury and fibrosis. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 17 31431059
2021 Monitoring basal autophagy in the retina utilizing CAG-mRFP-EGFP-MAP1LC3B reporter mouse: technical and biological considerations. Autophagy 15 34674604
2021 miR-451-3p alleviates myocardial ischemia/reperfusion injury by inhibiting MAP1LC3B-mediated autophagy. Inflammation research : official journal of the European Histamine Research Society ... [et al.] 12 34633468
2022 Genome-Wide Identification and Functional Characterization Reveals the Pivotal Roles of BnaA8.ATG8F in Salt Stress Tolerance and Nitrogen Limitation Adaptation in Allotetraploid Rapeseed. International journal of molecular sciences 10 36232619
2021 Ovarian Toxicity Induced by Aluminum Chloride: Alteration of Cyp19a1, Pcna, Puma, and Map1lc3b genes Expression. Toxicology 10 34958889
2018 Basal level of autophagy and MAP1LC3B-II as potential biomarkers for DHA-induced cytotoxicity in colorectal cancer cells. The FEBS journal 10 29723445
2023 Role of autophagy-related proteins ATG8f and ATG8h in the maintenance of autophagic activity in Arabidopsis roots under phosphate starvation. Frontiers in plant science 9 37434600
2015 Monitoring the Localization of MAP1LC3B by Indirect Immunofluorescence. Cold Spring Harbor protocols 8 26240409
2024 m6A RNA methylation modulates autophagy by targeting Map1lc3b in bisphenol A induced Leydig cell dysfunction. Journal of hazardous materials 7 39662354
2020 Monitoring the autophagy-endolysosomal system using monomeric Keima-fused MAP1LC3B. PloS one 6 32511278
2025 Histone deacetylase 6 inhibition attenuates pathological cardiac hypertrophy by promoting autophagy through MAP1LC3B ubiquitination. The Journal of pathology 5 40212005
2023 ATG8f Interacts with Chilli Veinal Mottle Virus 6K2 Protein to Limit Virus Infection. Viruses 5 38140565
2023 IGF2BP1/IMP1 Deletion Enhances a Facultative Stem Cell State via Regulation of MAP1LC3B. Cellular and molecular gastroenterology and hepatology 4 38081361
2022 SQSTM1 and its MAP1LC3B-binding domain induce forced mitophagy to degrade mitochondrial carryover during mitochondrial replacement therapy. Autophagy 4 35574946
2021 Combined Evaluation of MAP1LC3B and SQSTM1 for Biological and Clinical Significance in Ductal Carcinoma of Breast Cancer. Biomedicines 3 34829743
2025 HNRNPH1 promotes autophagy to inhibit the development of lung adenocarcinoma via the HSP90AB1/MAP1LC3B axis. Respiratory research 2 40468317
2025 Autophagy regulates the maternal-to-zygotic transition through MAP1LC3B-mediated maternal mRNA decay. Autophagy 2 41231099
2022 Association of CFH and MAP1LC3B gene polymorphisms with age-related macular degeneration in a high-altitude population. International journal of ophthalmology 1 36404982
2026 Urinary mRNA profiling of autophagy-related genes ATG5, ATG7, MAP1LC3B, and mTOR in non-muscle invasive bladder cancer (NMIBC). Cancer treatment and research communications 0 42044567