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The Atg12-Atg5 Conjugate Has a Novel E3-like Activity for Protein Lipidation in Autophagy
Open accessAbstract
Autophagy is a bulk degradation process in eukaryotic cells; autophagosomes enclose cytoplasmic components for degradation in the lysosome/vacuole. Autophagosome formation requires two ubiquitin-like conjugation systems, the Atg12 and Atg8 systems, which are tightly associated with expansion of autophagosomal membrane. Previous studies have suggested that there is a hierarchy between these systems; the Atg12 system is located upstream of the Atg8 system in the context of Atg protein organization. However, the concrete molecular relationship is unclear. Here, we show using an in vitro Atg8 conjugation system that the Atg12-Atg5 conjugate, but not unconjugated Atg12 or Atg5, strongly enhances the formation of the other conjugate, Atg8-PE. The Atg12-Atg5 conjugate promotes the transfer of Atg8 from Atg3 to the substrate, phosphatidylethanolamine (PE), by stimulating the activity of Atg3. We also show that the Atg12-Atg5 conjugate interacts with both Atg3 and PE-containing liposomes. These results indicate that the Atg12-Atg5 conjugate is a ubiquitin-protein ligase (E3)-like enzyme for Atg8-PE conjugation reaction, distinctively promoting protein-lipid conjugation.
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“Two ubiquitin-like conjugation systems also contribute to autophagosome formation [23,24,25].”
From LC3-Associated Phagocytosis (LAP): Connections with Host Autophagy (2012) · cites this paper as [25]
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BackgroundAutophagic activity in neuronal cell death
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“The Atg5-Atg12 protein conjugation is essential for the formation of LC3-IIpositive autophagosomes, with LC3-II being a key marker for autophagosomes (37).”
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Abernathy, E., Mateo, R., Majzoub, K., van Buuren, N. J., Bird, S. W., Carette, J. E., & Kirkegaard, K. (2019) · PLoS Biology · doi:10.1371/journal.pbio.2006926 · Cited by 87
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“Two ubiquitin-like conjugation systems facilitate elongation of the phagophore; namely, the Atg12–Atg5–ATG16L and Atg4B–Atg3–Atg7 complexes [19, 20].”
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Evasion of autophagy mediated by Rickettsia surface protein OmpB is critical for virulence
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The Role of Ceramide Metabolism and Signaling in the Regulation of Mitophagy and Cancer Therapy
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“This accumulation of ceramide on mitochondria allowed C18-ceramide to directly bind the hydrophobic domain (specifically Ile35 and Phe52) of LC3II on the phagophore to facilitate enclosure of the mitochondria by the autophagosome [6].”
BackgroundInfluentialAutophagy in plants and phytopathogens
Yoshimoto, K., Takano, Y., & Sakai, Y. (2010) · FEBS Letters · doi:10.1016/j.febslet.2010.01.007 · Cited by 84
“Recently, this complex was shown to function as an E3-like enzyme during Atg8 lipidation [22,23].”
BackgroundATG Systems from the Protein Structural Point of View
Noda, N. N., Ohsumi, Y., & Inagaki, F. (2009) · Chemical Reviews · doi:10.1021/cr800459r · Cited by 79
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“The CUMS model is widely used in depression studies, with the two main methods of the depression model including stress during pregnancy (7, 22, 23) and stress prior to pregnancy (4).”
BackgroundMethodMinocycline inhibits the growth of glioma by inducing autophagy
Liu, W., Lin, C.-H., Hsiao, M., & Gean, P. (2011) · Autophagy · doi:10.4161/auto.7.2.14043 · Cited by 78
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Kiel, J. A. K. W. (2010) · Philosophical Transactions of the Royal Society B Biological Sciences · doi:10.1098/rstb.2009.0237 · Cited by 80
Effects of tetrahedral DNA nanostructures on autophagy in chondrocytes
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“Atg14 – Atg15 – Atg16 Atg16L1 Part of Atg12-Atg5-Atg16 complex [69] Elongation Atg16L2 Atg17 FIP200 ULK-Atg13-FIP200 complex [67] Nucleation Atg18 Atg18A Atg18B Atg19 – – – Atg20 – – – Atg21 – – – Atg22 – – – Atg23 – – – Atg24 Atg24A – – Atg24B – – Atg25 – – – Atg26 – – – Atg27 – – – Atg28 – – – Atg29 – – – Vps15 Vps1…”
What Can Plant Autophagy Do for an Innate Immune Response?
Hayward, A. P., & Dinesh‐Kumar, S. P. (2011) · Annual Review of Phytopathology · doi:10.1146/annurev-phyto-072910-095333 · Cited by 78
Quantitative analysis of autophagy reveals the role of ATG9 and ATG2 in autophagosome formation
Broadbent, D. G., Barnaba, C., Perez, G. I., & Schmidt, J. C. (2023) · The Journal of Cell Biology · doi:10.1083/jcb.202210078 · Cited by 82
“…complex (Fracchiolla et al., 2020; Lystad et al., 2019), which acts similarly to ubiquitin ligase complexes but instead conjugates ATG8 family (e.g., LC3 and GABARAP) proteins to phosphatidyleth-anolamine at the phagophore membrane (Hanada et al., 2007; Kirisako et al., 1999; Shpilka et al., 2011).”
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“ATG12–ATG5 directly associates with ATG16 and forms a large complex through ATG16 oligomerization, which may function as an E3-like enzyme to catalyze the last step of ATG8-PE production (Hanada et al. 2007; Romanov et al. 2012).”
BackgroundStructural Insights into Atg10-Mediated Formation of the Autophagy-Essential Atg12-Atg5 Conjugate
Yamaguchi, M., Noda, N. N., Yamamoto, H., Shima, T., Kumeta, H., Kobashigawa, Y., Akada, R., Ohsumi, Y., & Inagaki, F. (2012) · Structure · doi:10.1016/j.str.2012.04.018 · Cited by 78
“The catalytic structures of KmAtg10, Atg3, and Ubc9-RanGAP1 were overlaid by minimizing the root-mean-square difference of the Ca atom of KmAtg10 Tyr56, Asn114, and Cys116 with that of the equivalent residue (Tyr87, Asp127, and Cys93 of Ubc9) using the CNS program.”
BackgroundInfluentialSelf-citationThe T300A Crohn’s disease risk polymorphism impairs function of the WD40 domain of ATG16L1
Boada-Romero, E., Serramito-Gómez, I., Sacristán, M. P., Boone, D. L., Xavier, R. J., & Pimentel‐Muiños, F. X. (2016) · Nature Communications · doi:10.1038/ncomms11821 · Cited by 80
“In this complex, the dimer ATG5-ATG12 holds the lipidating activity 26 , whereas ATG16L1 defines the site where LC3 will be lipidated 24 .”
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The Role of ATG16 in Autophagy and The Ubiquitin Proteasome System
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BackgroundInfluentialCufí, S., Vázquez‐Martín, A., Oliveras‐Ferraros, C., Corominas-Faja, B., Urruticoechea, A., Martı́n-Castillo, B., & Menéndez, J. A. (2012) · Oncotarget · doi:10.18632/oncotarget.742 · Cited by 75
Mechanisms of Autophagy in Metabolic Stress Response
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“Importantly, the ATG16L complex with ATG5-ATG12 has been demonstrated to provide an E3-like activity that promotes the lipidation of ATG8/LC3 [25,31].”
MiR-200b regulates autophagy associated with chemoresistance in human lung adenocarcinoma
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“This complex acts as an E3-like enzyme to facilitate ATG8-PE formation [10].”
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“In addition, the ATG12–ATG5 conjugate also serves as an E3 ligase, mediates the lipidation of MAP1LC3/LC3 (a major ortholog family of yeast Atg8) with phosphatidylethanolamine.(64) Genetic and in vitro studies indicate that the level of ATG12–ATG5 conjugate is essential for autophagic activity.”
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“As noted, the targeting of LC3-II to phagophores requires another conjugation system, in which ATG12-ATG5 complexes are noncovalently linked with ATG16L to form a multimeric complex (84, 85).”
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“Although the Atg12–5–16L1 complex has recently been shown to have E3-like enzyme activity toward LC3 (Hanada et al., 2007; Fujita et al., 2008a), since no LC3 signals were observed on dense-core vesicles (Figure 2A, bottom), the Atg12–5–16L1 complex together with Rab33A may have additional function other than E3-like…”
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BackgroundSelf-citationThe roles and functions of Paneth cells in Crohn’s disease: A critical review
Yang, E., & Shen, J. (2020) · Cell Proliferation · doi:10.1111/cpr.12958 · Cited by 77
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“This complex catalyzes the conjugation of the C-terminal Gly of ATG8 to phosphatidylethanolamine (PE) via ATG3 to promote incorporation of ATG8–PE (MAP1LC3B) into autophagosomes, thereby allowing autophagosome closure and cargo recruitment.(21) Knockouts of the Atg5 gene lead to ablation of ATG5-dependent autophagy.”
Scharl, M. M., Wojtal, K. A., Becker, H. M., Fischbeck, A., Frei, P., Arikkat, J. M., Pesch, T., Kellermeier, S., Boone, D. L., Weber, A., et al. (2011) · Inflammatory Bowel Diseases · doi:10.1002/ibd.21891 · Cited by 71
“13 The resulting ATG5-ATG12 conjugate is stabilized by a noncovalent complex with ATG16L1.”
BackgroundInfluentialAutophagic clearance of bacterial pathogens: molecular recognition of intracellular microorganisms
Pareja, M. E. M., & Colombo, M. I. (2013) · Frontiers in Cellular and Infection Microbiology · doi:10.3389/fcimb.2013.00054 · Cited by 75
“LIRs consist of a beta-strand containing the WxxL motif that forms an intermolecular beta-sheet with Atg8/LC3 (Noda et al., 2010).”
BackgroundAnandhan, A., Rodríguez‐Rocha, H., Bohovych, I., Griggs, A. M., Zavala-Flores, L. M., Reyes‐Reyes, E. M., Seravalli, J., Stanciu, L., Lee, J., Rochet, J., et al. (2014) · Neurobiology of Disease · doi:10.1016/j.nbd.2014.11.018 · Cited by 73
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“ubiquitin-like enzyme) forms a complex with Atg16 and functions with Atg7 (an E1) and Atg3 (an E2) to conjugate LC3-1 with phosphatidylethanolamine (PE) [35–39].”
BackgroundThe roles of autophagy in development and stress responses in Arabidopsis thaliana
Lv, X., Pu, X., Qin, G., Zhu, T., & Lin, H. (2014) · APOPTOSIS · doi:10.1007/s10495-014-0981-4 · Cited by 70
“Their dynamics in vivo suggest that formation of the ATG12– ATG5 conjugate precedes formation of the ATG8–PE conjugate, and enhances this lipidation reaction via crosstalk between the two conjugation reactions [114, 115].”
BackgroundMacroautophagy and Chaperone‐Mediated Autophagy in Heart Failure: The Known and the Unknown
Ghosh, R., & Pattison, J. S. (2018) · Oxidative Medicine and Cellular Longevity · doi:10.1155/2018/8602041 · Cited by 72
“Cleaved Atg8 is then transferred to Atg3 (an E2-like homolog) along with Atg7 which adds a phosphatidylethanolamine (PE) group to Atg8, which is also facilitated by Atg12-Atg5-Atg16 complex which behaves as an E3like ligase [40, 41].”
BackgroundAutophagy: The multi‐purpose bridge in viral infections and host cells
Abdoli, A., Alirezaei, M., Mehrbod, P., & Forouzanfar, F. (2018) · Reviews in Medical Virology · doi:10.1002/rmv.1973 · Cited by 69
“The third pathway that contributes to autophagosome formation and elongation involves ubiquitin‐like conjugation processes that generate membrane‐bound protein complexes.(30) Atg7 and Atg10 mediate the conjugation of Atg12 to Atg5, which subsequently interact with Atg16.”
BackgroundSatyavarapu, E. M., Das, R., Mandal, C., Mukhopadhyay, A., & Mandal, C. (2018) · Cell Death & Disease · doi:10.1038/s41419-018-0989-8 · Cited by 69
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“Antisera against Ape1 ( Klionsky et al., 1992 ) and Atg8 ( Huang et al., 2000 ) have been described previously.”
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“ATG16L1 and TECPR1 bind to ATG5 via a conserved motif within an a-helix Although ATG16N69 and TECAIR exhibit structural differences in their overall binding to ATG5, they adopt a similar a-helical structure, which was originally described in the Saccharomyces cerevisiae Atg5-Atg16 (1–57) structure (Fig.”
BackgroundInfluentialMechanism of cargo-directed Atg8 conjugation during selective autophagy
Fracchiolla, D., Sawa-Makarska, J. Z., Zens, B., de Ruiter, A., Zaffagnini, G., Brezovich, A., Romanov, J., Runggatscher, K., Kraft, C., Žagrović, B., et al. (2016) · eLife · doi:10.7554/elife.18544 · Cited by 69
“The Atg12~Atg5-Atg16 complex acts in an E3-like manner and determines the site of Atg8 conjugation (Fujita et al., 2008b; Hanada et al., 2007).”
BackgroundWu, H., Pu, J., Krafft, P. R., Zhang, J., & Chen, S. (2014) · Cellular and Molecular Neurobiology · doi:10.1007/s10571-014-0116-z · Cited by 72
“Actually, LC3 plays an important role in mediating membrane tethering and hemifusion, which, in turn, is crucial for the expansion and fusion of the autophagosomal membrane during the process of autophagy (Geng and Klionsky 2008; Hanada et al. 2007; Nakatogawa et al. 2007).”
BackgroundKumar, D., Das, B., Sen, R., Kundu, P., Manna, A., Sarkar, A., Chowdhury, C., Chatterjee, M., & Das, P. (2015) · PLoS ONE · doi:10.1371/journal.pone.0139657 · Cited by 68
“Atg 5 has been characterized as an ubiquitin-like protein involved in autophagosome formation [43].”
BackgroundAgrotis, A., von Chamier, L., Oliver, H., Kiso, K., Singh, T., & Ketteler, R. (2019) · Journal of Biological Chemistry · doi:10.1074/jbc.ac119.009977 · Cited by 69
Mechanism and Regulation of Autophagy and Its Role in Neuronal Diseases
Hu, Z., Yang, B., Mo, X., & Xiao, H. (2014) · Molecular Neurobiology · doi:10.1007/s12035-014-8921-4 · Cited by 69
“modulate LC3-I conjugation to PE by acting in an E3-like fashion [89] and the location of the Atg5-Atg12:Atg16L complex at the phagophore dictates the location of the LC3 con-”
BackgroundYen, J.-H., Wu, P.-S., Chen, S., & Wu, M. (2017) · International Journal of Molecular Sciences · doi:10.3390/ijms18040852 · Cited by 68
“The formation of Atg12–Atg5 conjugate is a key factor in regulating the formation of autophagosome [38].”
BackgroundSignaling and other functions of lipids in autophagy: a review
Soto-Avellaneda, A., & Morrison, B. E. (2020) · Lipids in Health and Disease · doi:10.1186/s12944-020-01389-2 · Cited by 71
Iriondo, M. N., Etxaniz, A., Varela, Y. R., Ballesteros, U., Lázaro, M., Valle, M., Fracchiolla, D., Martens, S., Montes, L. R., Goñi, F. M., et al. (2023) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-023-04704-z · Cited by 73
“In vitro studies with yeast proteins have investigated the interplay between both ubiquitin-like systems and their interaction with membranes [11, 12, 37] showing that the presence of yeast E3 (Atg12–Atg5-Atg16), increased Atg3 activity, boosting the lipid-protein conjugation reaction and specifying the membrane site…”
BackgroundKwon, S. I., & Park, O. K. (2008) · Journal of Plant Biology · doi:10.1007/bf03036132 · Cited by 68
“The ATG8-PE conjugate requires the protease ATG4, whereas the ATG12ATG5 conjugate forms a multimeric complex with ATG16 (Ohsumi, 2001; Kuma et al., 2002; Hanada et al., 2007).”
BackgroundGarcía‐García, A., Anandhan, A., Burns, M., Chen, H., Zhou, Y., & Franco, R. (2013) · Toxicological Sciences · doi:10.1093/toxsci/kft188 · Cited by 65
“The Atg12-Atg5 complex conjugation is essential for autophagosome formation, and functions as an E3-like ligase for LC3 lipidation (Hanada et al., 2007; Tanida, 2011) (Fig.”
BackgroundSun, L., Liu, A., Zhang, J., Ji, W., Li, Y., Yang, X., Wu, Z., & Guo, J. (2016) · Behavioural Brain Research · doi:10.1016/j.bbr.2016.09.020 · Cited by 67
Regulation of Exercise-Induced Autophagy in Skeletal Muscle
Rocchi, A., & He, C. (2017) · Current Pathobiology Reports · doi:10.1007/s40139-017-0135-9 · Cited by 69
Mapping Autophagy on to Your Metabolic Radar
Yamada, E., & Singh, R. (2012) · Diabetes · doi:10.2337/db11-1199 · Cited by 67
“In ensuing reactions requiring Atg5-Atg12 (13), LC3 is lipidated to membrane-associated phosphatidylethanolamine.”
BackgroundLieberman, O. J., & Sulzer, D. (2019) · Journal of Molecular Biology · doi:10.1016/j.jmb.2019.12.028 · Cited by 66
“The Atg5-12 conjugate subsequently interacts with Atg16L1 [47].”
BackgroundNoh, H. S., Hah, Y., Zada, S., Ha, J. H., Sim, G., Hwang, J. S., Lai, T. H., Nguyen, H. Q., Park, J., Kim, H. J., et al. (2016) · Autophagy · doi:10.1080/15548627.2016.1219013 · Cited by 65
Optineurin provides a mitophagy contact site for TBK1 activation
Yamano, K., Sawada, M., Kikuchi, R., Nagataki, K., Kojima, W., Endo, R., Kinefuchi, H., Sugihara, A., Fujino, T., Watanabe, A., et al. (2024) · The EMBO Journal · doi:10.1038/s44318-024-00036-1 · Cited by 68
“Since LC3B lipidation is catalyzed by ATG5, but not by FIP200 or ATG9A, the lipidated form is absent only in ATG5 KO cells (Hanada et al, 2007).”
BackgroundReggiori, F., Komatsu, M., Finley, K. D., & Simonsen, A. (2012) · International Journal of Cell Biology · doi:10.1155/2012/156272 · Cited by 68
“On one hand, the multimeric Atg12-Atg5Atg16 complex localizes to the phagophore and acts as an E3-like enzyme, determining the site of Atg8/LC3 lipidation [47, 48].”
BackgroundNeuronal autophagy in cerebral ischemia
Xu, F., Gu, J., & Qin, Z. (2012) · Neuroscience Bulletin · doi:10.1007/s12264-012-1268-9 · Cited by 66
“[47] Hanada T, Noda NN, Satomi Y, Ichimura Y, Fujioka Y, Takao T, et al.”
BackgroundEmerging roles of autophagy in metabolism and metabolic disorders
Rocchi, A., & He, C. (2015) · Frontiers in Biology · doi:10.1007/s11515-015-1354-2 · Cited by 66
Lipid Geometry and Bilayer Curvature Modulate LC3/GABARAP-Mediated Model Autophagosomal Elongation
Landajuela, A., Hervás, J. H., Antón, Z., Montes, L. R., Gil, D., Valle, M., Rodriguez, J. F., Goñi, F. M., & Alonso, A. (2016) · Biophysical Journal · doi:10.1016/j.bpj.2015.11.3524 · Cited by 69
“However, both systems are essential for proper AP biogenesis in vivo, and several in vitro studies (61,62) indicated that the ATG12ATG5-ATG16L1 complex functions, at least in part, facilitating the transfer of ATG8/LC3 from ATG3 to PE.”
BackgroundSpecific autophagy and ESCRT components participate in the unconventional secretion of CFTR
Noh, S. H., Gee, H. Y., Kim, Y., Piao, H., Kim, J., Kang, C., Lee, G., Mook‐Jung, I., Lee, Y., Cho, J. W., et al. (2018) · Autophagy · doi:10.1080/15548627.2018.1489479 · Cited by 66
Epigenetic modifications of autophagy in cancer and cancer therapeutics
Bhol, C. S., Panigrahi, D. P., Praharaj, P. P., Mahapatra, K. K., Patra, S., Mishra, S. R., Behera, B. P., & Bhutia, S. K. (2019) · Seminars in Cancer Biology · doi:10.1016/j.semcancer.2019.05.020 · Cited by 67
Gestational exercise protects adult male offspring from high-fat diet-induced hepatic steatosis
Sheldon, R. D., Blaize, A. N., Fletcher, J. A., Pearson, K. J., Donkin, S. S., Newcomer, S. C., & Rector, R. S. (2015) · Journal of Hepatology · doi:10.1016/j.jhep.2015.08.022 · Cited by 68
“The ATG12:5 conjugate resides on isolation membranes (pre-autophagic structures) [29] and catalyzes the conjugation of LC3 to phosphatidylethanolamine [30], which is the necessary committed step to mature autophagosome formation [31].”
BackgroundZou, J., Yue, F., Jiang, X., Li, W., Yi, J., & Liu, L. (2013) · Biochemical Journal · doi:10.1042/bj20130306 · Cited by 65
MnSOD Upregulation Induces Autophagic Programmed Cell Death in Senescent Keratinocytes
Deruy, E., Gosselin, K., Vercamer, C., Martien, S., Bouali, F., Slomianny, C., Bertout, J., Bernard, D., Pourtier, A., & Abbadie, C. (2010) · PLoS ONE · doi:10.1371/journal.pone.0012712 · Cited by 67
“in the lipidation of Atg8/LC3 [23] and hence in autophagosome”
BackgroundAutophagy as a Possible Underlying Mechanism of Nanomaterial Toxicity
Cohignac, V., Landry, M., Boczkowski, J., & Lanone, S. (2014) · Nanomaterials · doi:10.3390/nano4030548 · Cited by 70
“It has been shown that the Atg12-Atg5 conjugate can have an E3 ubiquitin ligase activity to facilitate LC3 conjugation [113].”
BackgroundChemotherapy Resistance: Role of Mitochondrial and Autophagic Components
Bahar, E., Han, S., Kim, J., & Yoon, H. (2022) · Cancers · doi:10.3390/cancers14061462 · Cited by 67
A novel ER-localized transmembrane protein, EMC6, interacts with RAB5A and regulates cell autophagy
Li, Y., Zhao, Y., Hu, J. N., Xiao, J., Qu, L., Wang, Z., Ma, D., & Chen, Y. (2012) · Autophagy · doi:10.4161/auto.22742 · Cited by 66
“The Atg12–Atg5 conjugate apparently has an E3-like activity for Atg8 lipidation.(8)”
BackgroundMicro RNA ‐214‐3p: A link between autophagy and endothelial cell dysfunction in atherosclerosis
Wang, J., Wang, W. ‐., Xu, S., Wu, H., Dai, B., Jian, D., Yang, M., Wu, Y. ‐., Feng, Q., Zhu, J., et al. (2017) · Acta Physiologica · doi:10.1111/apha.12973 · Cited by 63
“The ATG12 system is comprised of the ATG12ATG5 complex, located upstream of the LC3 system, which significantly improved the formation of LC3-phosphatidylethanolamine (LC-PE) conjugation.(21) The relationship between miRNA and ATG5 has been reported several times in other diseases.”
BackgroundDelorme‐Axford, E., & Klionsky, D. J. (2018) · Journal of Biological Chemistry · doi:10.1074/jbc.r117.804641 · Cited by 63
Autophagy in plant pathogenic fungi
Liu, X., Xu, F., Snyder, J. H., Shi, H., Lu, J., & Lin, F. (2016) · Seminars in Cell and Developmental Biology · doi:10.1016/j.semcdb.2016.03.022 · Cited by 62
Mammalian autophagy and the plasma membrane
Tanasa, M. P., & Rubinsztein, D. C. (2016) · FEBS Journal · doi:10.1111/febs.13931 · Cited by 64
Atg8 regulates vacuolar membrane dynamics in a lipidation-independent manner in Pichia pastoris
Tamura, N., Oku, M., & Sakai, Y. (2010) · Journal of Cell Science · doi:10.1242/jcs.070045 · Cited by 68
“Recently, this complex was shown to function as an E3-like enzyme during Atg8 lipidation (Fujita et al., 2008; Hanada et al., 2007).”
BackgroundThe lifecycle of skeletal muscle mitochondria in obesity
Pileggi, C. A., Parmar, G., & Harper, M. (2021) · Obesity Reviews · doi:10.1111/obr.13164 · Cited by 61
“aiding in the conjugation of LC3-I to phosphatidylethanolamine (PE) on the phagophore membrane.(144,148,149) LC3-I is converted to a”
BackgroundDisruption of Endoplasmic Reticulum and ROS Production in Human Ovarian Cancer by Campesterol
Bae, H., Park, S., Yang, C., Song, G., & Lim, W. (2021) · Antioxidants · doi:10.3390/antiox10030379 · Cited by 65
“In addition, autophagy-related gene are reported as tumor suppressor including BECN1 and Atg5 [40].”
BackgroundNoncanonical recognition and UBL loading of distinct E2s by autophagy-essential Atg7
Yamaguchi, M., Matoba, K., Sawada, R., Fujioka, Y., Nakatogawa, H., Yamamoto, H., Kobashigawa, Y., Hoshida, H., Akada, R., Ohsumi, Y., et al. (2012) · Nature Structural & Molecular Biology · doi:10.1038/nsmb.2451 · Cited by 62
Self-citationImpact of cellular autophagy on viruses: Insights from hepatitis B virus and human retroviruses
Tang, S.-W., Ducroux, A., Jeang, K., & Neuveut, C. (2012) · Journal of Biomedical Science · doi:10.1186/1423-0127-19-92 · Cited by 63
“The Atg12-Atg5-Atg16L1 complex has been reported to guide LC3-I to the phagophore membrane, and to function as E3-like ubiquitin ligase to promote the lipidation of LC3-I by PE [32,33].”
Background
Metadata
- Authors
- Hanada, T., Noda, N. N., Satomi, Y., Ichimura, Y., Fujioka, Y., Takao, T., Inagaki, F., & Ohsumi, Y.
- Affiliations
- National Institute for Basic Biology (JP)
- Hokkaido University (JP)
- Institute for Protein Research, The University of Osaka (JP)
- Corresponding author
- Ohsumi, Yoshinori
- ORCID
- Venue
- Journal of Biological Chemistry
- Publisher
- Elsevier BV
- Published
- 2007-12
- Volume
- 282
- Issue
- 52
- Pages
- 37298-37302
- ISSN
- 0021-9258 (ISSN-L)
- OpenAlex
- W2040157483
- Semantic Scholar
- ac42037b48b9d80a5e5c15efd2379440ed23b91c
- Cited by
- 1,123
- References
- 28
- Citations by year
- 2026: 31 · 2025: 38 · 2024: 44 · 2023: 55 · 2022: 59 · 2021: 68 · 2020: 75 · 2019: 87 · 2018: 61 · 2017: 54 · 2016: 79 · 2015: 77 · 2014: 64 · 2013: 65 · 2012: 81
- FWCI
- 28.90
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Biological Chemistry (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Tokyo Tech Research Repository (Tokyo Institute of Technology) (submittedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Autophagy in Disease and Therapy
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Ubiquitin and proteasome pathways
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular transport and secretion
- Keywords
- ATG12-ATG5 conjugate, protein lipidation, E3 ubiquitin ligase activity, autophagy, ATG3, ATG12, ATG8, phosphatidylethanolamine, autophagosome formation, liposome binding
- MeSH terms
- Autophagy-Related Protein 5, Autophagy-Related Protein 12, Autophagy, Escherichia coli, Lipids, Liposomes, Models, Biological, Protein Processing, Post-Translational, Saccharomyces cerevisiae, Time Factors, Gene Expression Regulation, Fungal, Ubiquitin, Saccharomyces cerevisiae Proteins, Ubiquitin-Protein Ligases
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