The DOI matches its Crossref record; 28 of the 28 references it cites were found in a registry or an index.
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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“The yeast Atg12-Atg5 conjugate functions in vitro as an E3like enzyme for Atg8 lipidation (62).”
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“Although Atg16 is not important for efficient Atg8–PE conjugation in vitro, it is required for Atg8–PE formation in vivo [303].”
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Huang, J., Lam, G. Y., & Brumell, J. H. (2010) · Antioxidants and Redox Signaling · doi:10.1089/ars.2010.3554 · Cited by 228
“Under the activity of Atg7, Atg3 (another E2-like enzyme) and Atg12-Atg5 complex (acts as an E3), Atg8 = LC3 is attached to the phospholipid PE and remains on the autophagosomal membrane throughout the autophagy process (47, 57, 65).”
Bhutia, S. K., Mukhopadhyay, S., Sinha, N., Das, D. N., Panda, P. K., Patra, S. K., Maiti, T. K., Mandal, M., Dent, P., Wang, X., et al. (2013) · Advances in cancer research · doi:10.1016/b978-0-12-407173-5.00003-0 · Cited by 241
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Monastyrska, I., Rieter, E., Klionsky, D. J., & Reggiori, F. (2009) · Biological reviews/Biological reviews of the Cambridge Philosophical Society · doi:10.1111/j.1469-185x.2009.00082.x · Cited by 234
“Activation of the Atg12 conjugation system triggers the Atg8 conjugation system that directs the association of Atg8 to the PAS, after being conjugated to phosphatidylethanolamine (PE); Atg12–Atg5-Atg16 may function as an E3 ubiquitin ligase, and Atg16 appears to target the site of Atg8–PE formation (Fujita et al., 20…”
Vesicular trafficking and autophagosome formation
Longatti, A., & Tooze, S. A. (2009) · Cell Death and Differentiation · doi:10.1038/cdd.2009.39 · Cited by 226
“a novel E3-like enzyme allowing the recruitment of the Atg3 (E2)-LC3 intermediate to the substrate PE in the membrane, thus determining the site of LC3 lipidation.(6,7) Elongation of the IM requires the Atg16L complex(8) and LC3-II/Atg8-PE.”
BackgroundAutophagy and cancer – issues we need to digest
Liu, E. Y., & Ryan, K. M. (2012) · Journal of Cell Science · doi:10.1242/jcs.093708 · Cited by 225
“1) (Fujita et al., 2008; Hanada et al., 2007; Sou et al., 2008; Xie and Klionsky, 2007).”
Epigenetic Regulation of Autophagy by the Methyltransferase G9a
de Narvajas, A. A.-M., Gomez, T. S., Zhang, J., Mann, A. O., Taoda, Y., Gorman, J. A., Herreros‐Villanueva, M., Gress, T. M., Ellenrieder, V., Bujanda, L., et al. (2013) · Molecular and Cellular Biology · doi:10.1128/mcb.00813-13 · Cited by 217
“In order to determine whether autophagosomes induced upon G9a inhibition utilized the canonical pathway for formation, we examined LC3B-II conversion in ATG5-deficient MEFs, a key regulator of this process (32, 33).”
BackgroundNon-canonical autophagy drives alternative ATG8 conjugation to phosphatidylserine
Durgan, J., Lystad, A. H., Sloan, K., Carlsson, S. R., Wilson, M. I., Marcassa, E., Ulferts, R., Webster, J. A., Lopez‐Clavijo, A. F., Wakelam, M. J. O., et al. (2021) · Molecular Cell · doi:10.1016/j.molcel.2021.03.020 · Cited by 217
The paradox of autophagy and its implication in cancer etiology and therapy
Eisenberg‐Lerner, A., & Kimchi, A. (2009) · APOPTOSIS · doi:10.1007/s10495-008-0307-5 · Cited by 220
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“Both contribute to the expansion and the closure of the vesicle in concert with two ubiquitin-like conjugation systems, resulting in the ATG12–ATG5-ATG16L complex and the phosphatidylethanolamine (PtdEtn) conjugate of microtubuleassociated protein 1 light chain 3 [LC3 (MLP3); the mammalian ortholog of Atg8 in budding…”
BackgroundA Mammalian Autophagosome Maturation Mechanism Mediated by TECPR1 and the Atg12-Atg5 Conjugate
Chen, D., Fan, W., Lu, Y., Ding, X., Chen, S., & Zhong, Q. (2012) · Molecular Cell · doi:10.1016/j.molcel.2011.12.036 · Cited by 221
“The Atg12-Atg5-Atg16 complex localizes to nascent autophagosomes (Mizushima et al., 2001, 2003) and functions upstream to the LC3 lipidation and its autophagosome targeting (Fujita et al., 2008; Hanada et al., 2007).”
Activation and targeting of ATG8 protein lipidation
Martens, S., & Fracchiolla, D. (2020) · Cell Discovery · doi:10.1038/s41421-020-0155-1 · Cited by 218
Gammoh, N., Florey, O., Overholtzer, M., & Jiang, X. (2012) · Nature Structural & Molecular Biology · doi:10.1038/nsmb.2475 · Cited by 213
Autophagy: An Intracellular Degradation Pathway Regulating Plant Survival and Stress Response
Su, T., Li, X., Yang, M., Shao, Q., Zhao, Y., Ma, C., & Wang, P. (2020) · Frontiers in Plant Science · doi:10.3389/fpls.2020.00164 · Cited by 211
“…(PC) editing and lipid desaturation in the anthers of these mutants during pollen maturation, indicating the involvement of autophagy in the regulation of lipid metabolism during plant development February 2020 | Volume 11 | Article 164 (Hanamata et al., 2014; Kurusu et al., 2014).”
BackgroundWei, M., Chen, M., Chen, K.-C., Lou, P., Lin, S. Y.-F., Hung, S., Hsiao, M., Yao, C.-J., & Shieh, M. (2014) · Autophagy · doi:10.4161/auto.28679 · Cited by 204
“ATG3 and ATG5 are both essential regulatory components of autophagosome biogenesis.(61,62) A recent report shows that ATG3 degradation by CASP8 could lead to autophagy inactivation during receptor-triggered apoptosis.”
Lipid droplets and their component triglycerides and steryl esters regulate autophagosome biogenesis
Shpilka, T., Welter, E., Borovsky, N., Amar, N., Mari, M. C., Reggiori, F., & Elazar, Z. (2015) · The EMBO Journal · doi:10.15252/embj.201490315 · Cited by 211
“Atg8 is a key player in autophagosome formation and is regulated by several essential autophagy factors that enable it to conjugate to phosphatidylethanolamine (PE) on the autophagic membrane (Kirisako et al , 2000; Suzuki et al , 2001; Hanada et al , 2007; Shpilka et al , 2012).”
Coordinated loading of IRG resistance GTPases on to the Toxoplasma gondii parasitophorous vacuole
Khaminets, A., Hunn, J. P., Könen‐Waisman, S., Zhao, Y. O., Preukschat, D., Coers, J., Boyle, J. P., Ong, Y.-C., Boothroyd, J. C., Reichmann, G., et al. (2010) · Cellular Microbiology · doi:10.1111/j.1462-5822.2010.01443.x · Cited by 204
“Which if any of the increasing range of activities attributed to Atg5 (Hanada et al., 2007; Geng and Klionsky, 2008) could be responsible for this activity is unclear.”
BackgroundIRGM Is a Common Target of RNA Viruses that Subvert the Autophagy Network
Grégoire, I. P., Richetta, C., Meyniel‐Schicklin, L., Borel, S., Pradezynski, F., Diaz, O., Deloire, A., Azocar, O., Baguet, J., Breton, M., et al. (2011) · PLoS Pathogens · doi:10.1371/journal.ppat.1002422 · Cited by 216
“The elongation of the isolation membrane involves two ubiquitin-like conjugation systems [6,7].”
BackgroundAcetylated microtubules are required for fusion of autophagosomes with lysosomes
Xie, R., Nguyen, S., McKeehan, W. L., & Liu, L. (2010) · BMC Cell Biology · doi:10.1186/1471-2121-11-89 · Cited by 195
“The LC3 precursor is truncated to LC3I then conjugated with phosphatidylethanolamine to membrane-associated LC3II mediated by the ATG5-ATG12 conjugate [4,5].”
BackgroundChung, T., Suttangkakul, A., & Vierstra, R. D. (2009) · Plant Physiology · doi:10.1104/pp.108.126714 · Cited by 221
“ATG8-PE assembly is stimulated in vitro by a complex containing the ATG12-ATG5 adduct and ATG16, suggesting that the ATG12-ATG5 adduct has an E3-like catalytic role in ATG8 conjugation (Hanada et al., 2007; Fujita et al., 2008).”
BackgroundAutophagy, cell death, and cancer
Lin, L., & Baehrecke, E. H. (2015) · Molecular & Cellular Oncology · doi:10.4161/23723556.2014.985913 · Cited by 206
Host immune responses to Toxoplasma gondii
Sasai, M., Pradipta, A., & Yamamoto, M. (2018) · International Immunology · doi:10.1093/intimm/dxy004 · Cited by 202
Autophagy: Regulation and role in disease
Meijer, A. J., & Codogno, P. (2009) · Critical Reviews in Clinical Laboratory Sciences · doi:10.1080/10408360903044068 · Cited by 215
“Both Atg5Atg12 and Atg8-PE are produced by two unique, ubiquitin-like conjugation systems: the formation of Atg5-Atg12 requires Atg7 (homologous to the E1 ubiquitin-activating enzyme) and Atg10 (homologous to the E2 ubiquitin-activating enzyme), whereas conjugation of PE with Atg8 (a ubiquitin-like protein) requires A…”
Rodríguez‐Rocha, H., García‐García, A., Panayiotidis, M. I., & Franco, R. (2011) · Mutation research. Fundamental and molecular mechanisms of mutagenesis · doi:10.1016/j.mrfmmm.2011.03.007 · Cited by 205
Temporal Regulation of Intracellular Organelle Homeostasis in T Lymphocytes by Autophagy
Jia, W., & He, Y.-W. (2011) · The Journal of Immunology · doi:10.4049/jimmunol.1002404 · Cited by 204
“However, this is independent of autophagy because the disruption of the conjugates of the Atg12 and Atg3 complex does not affect the starvation-induced autophagy (36).”
BackgroundInfluentialAutophagy in cellular metabolism and cancer
Jiang, X., Overholtzer, M., & Thompson, C. B. (2015) · Journal of Clinical Investigation · doi:10.1172/jci73942 · Cited by 202
“…LC3 is conjugated to phosphatidyl eth-anolamine (PE) instead of a protein, a process that is catalyzed by ATG7, E2-like ATG3, and the ATG12-ATG5 conjugate, which is considered to be an E3-like enzyme for LC3-PE conjugation (26, 27). the acetylation status of ATG proteins was not determined.”
The ubiquitin-proteasome system and autophagy: Coordinated and independent activities
Cohen‐Kaplan, V., Livneh, I., Avni, N., Cohen-Rosenzweig, C., & Ciechanover, A. J. (2016) · The International Journal of Biochemistry & Cell Biology · doi:10.1016/j.biocel.2016.07.019 · Cited by 205
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“…membranes and are required for the initiation and expansion of autophagosomal membrane and hemifusion of this membrane with the vacuolar membrane (Hanada et al., 2007; Nakatogawa et al., 2007, 2009; 1 This work was supported by the Spanish Ministry of Science and Innovation (grant no.”
BackgroundAutophagy: A novel mechanism of chemoresistance in cancers
Li, X., Zhou, Y., Li, Y., Yang, L., Ma, Y., Peng, X., Yang, S., Liu, J., & Li, H. (2019) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2019.109415 · Cited by 200
Emerging roles of ATG7 in human health and disease
Collier, J. J., Suomi, F., Oláhová, M., McWilliams, T. G., & Taylor, R. W. (2021) · EMBO Molecular Medicine · doi:10.15252/emmm.202114824 · Cited by 201
“Although LC3-II can be generated in vitro in the presence of ATG3, ATG7, LC3, ATP and liposomes containing PE, ATG5-ATG12 forms a complex with ATG16L that promotes LC3 lipidation in vivo (Mizushima et al, 1999, 2003; Kuma et al, 2002; Hanada et al, 2007; Lystad et al, 2019).”
BackgroundAutophagy in Neuroprotection and Neurodegeneration: A Question of Balance
Cherra, S. J., & Chu, C. T. (2008) · Future Neurology · doi:10.2217/14796708.3.3.309 · Cited by 194
“Atg5 - this protein is covalently conjugated to Atg12 in a ubiquitin-like conjugation reaction, and may play an E3-like role in promoting efficient LC3 lipidation [102].”
BackgroundStephenson, L. M., Miller, B. C., Ng, A., Eisenberg, J. M., Zhao, Z., Cadwell, K., Graham, D. B., Mizushima, N., Xavier, R. J., Virgin, H. W., et al. (2009) · Autophagy · doi:10.4161/auto.5.5.8133 · Cited by 200
Atomistic Autophagy: The Structures of Cellular Self-Digestion
Hurley, J. H., & Schulman, B. A. (2014) · Cell · doi:10.1016/j.cell.2014.01.070 · Cited by 197
“Atg8/LC3 is subsequently transferred to PE in a reaction facilitated by the Atg12 5 conjugate acting as an E3 enzyme (Hanada et al., 2007).”
Autophagy-regulating protease Atg4: structure, function, regulation and inhibition
Maruyama, T., & Noda, N. N. (2018) · The Journal of Antibiotics · doi:10.1038/ja.2017.104 · Cited by 190
Self-citationLi, M., Khambu, B., Zhang, H., Kang, J. H., Chen, X., Chen, D., Vollmer, L. L., Liu, P.-Q., Vogt, A., & Yin, X. (2013) · Journal of Biological Chemistry · doi:10.1074/jbc.m113.511212 · Cited by 186
Gorbea, C. M., Makar, K. A., Pauschinger, M., Pratt, G. W., Bersola, J., Varela, J. J., David, R. M., Banks, L. D., Huang, C., Li, H., et al. (2010) · Journal of Biological Chemistry · doi:10.1074/jbc.m109.047464 · Cited by 192
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Miura, K., & Hasegawa, P. M. (2010) · Trends in Cell Biology · doi:10.1016/j.tcb.2010.01.007 · Cited by 191
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Martinet, W., Agostinis, P., Vanhoecke, B., Dewaele, M., & de Meyer, G. R. Y. (2009) · Clinical Science · doi:10.1042/cs20080508 · Cited by 186
Mammalian macroautophagy at a glance
Ravikumar, B., Futter, M., Jahreiss, L., Korolchuk, V. I., Lichtenberg, M., Luo, S., Massey, D. C. O., Menzies, F. M., Narayanan, U., Renna, M., et al. (2009) · Journal of Cell Science · doi:10.1242/jcs.031773 · Cited by 196
“The Atg5-Atg12 conjugate seems to modulate LC3-I conjugation to PE by acting in an E3-like fashion (Hanada et al., 2007) and the Atg5-Atg12-Atg16L complex also determines the sites of LC3 lipidation (Fujita et al.”
BackgroundMartínez-López, N., Athonvarangkul, D., & Singh, R. (2015) · Advances in experimental medicine and biology · doi:10.1007/978-1-4939-2404-2_3 · Cited by 185
“1) resulting in membrane formation [23].”
Current knowledge of the pre‐autophagosomal structure (PAS)
Suzuki, K., & Ohsumi, Y. (2010) · FEBS Letters · doi:10.1016/j.febslet.2010.02.001 · Cited by 184
“Atg8 is conjugated to the phospholipid phosphatidylethanolamine (Atg8–PE) by serial reactions of Atg4 (an Atg8 processing enzyme), Atg7 (an E1-like protein), Atg3 (an E2-like protein), and Atg12–Atg5 (an E3-like conjugate) [39].”
BackgroundSelf-citationAccumulation of autophagosomes confers cytotoxicity
Button, R. W., Roberts, S. L., Willis, T. L., Hanemann, C. O., & Luo, S. (2017) · Journal of Biological Chemistry · doi:10.1074/jbc.m117.782276 · Cited by 186
The late stages of autophagy: how does the end begin?
Noda, T., Fujita, N., & Yoshimori, T. (2009) · Cell Death and Differentiation · doi:10.1038/cdd.2009.54 · Cited by 190
“added to the Atg8 in vitro reaction system, the reaction is accelerated.(25) Hence, localization of the Atg16L complex is a”
Membrane remodeling by the PX-BAR protein SNX18 promotes autophagosome formation
Knævelsrud, H., Søreng, K., Raiborg, C., Håberg, K., Rasmuson, F., Brech, A., Liestøl, K., Rusten, T. E., Stenmark, H., Neufeld, T. P., et al. (2013) · The Journal of Cell Biology · doi:10.1083/jcb.201205129 · Cited by 177
Viral strategies for triggering and manipulating mitophagy
Zhang, L., Qin, Y., & Chen, M. (2018) · Autophagy · doi:10.1080/15548627.2018.1466014 · Cited by 175
Taherbhoy, A. M., Tait, S. W. G., Kaiser, S. E., Williams, A. H., Deng, A., Nourse, A., Hammel, M., Kurinov, I. V., Rock, C. O., Green, D. R., et al. (2011) · Molecular Cell · doi:10.1016/j.molcel.2011.08.034 · Cited by 172
“Finally, Atg8 is transferred from Atg3’s catalytic cysteine to PE in a reaction stimulated by an unusual multiprotein E3 containing the Atg12 Atg5 complex (Hanada et al., 2007; Ichimura et al., 2000).”
BackgroundThe cellular pathways of neuronal autophagy and their implication in neurodegenerative diseases
Yue, Z., Friedman, L. G., Komatsu, M., & Tanaka, K. (2009) · Biochimica et Biophysica Acta (BBA) - Molecular Cell Research · doi:10.1016/j.bbamcr.2009.01.016 · Cited by 179
“The Atg5–Atg12·Atg16 complex is essential for autophagosome formation and facilitates Atg8 conjugation with PE [40] through E3-like activity of Atg5–Atg12 for Atg8 conjugation [42].”
BackgroundAutophagy and pattern recognition receptors in innate immunity
Delgado, M. A., Singh, S., Haro, S. A. D., Master, S. S., Ponpuak, M., Dinkins, C., Ornatowski, W., Vergne, I., & Deretic, V. P. (2008) · Immunological Reviews · doi:10.1111/j.1600-065x.2008.00725.x · Cited by 176
“1) The Atg5–Atg12 ⁄ 16 complex acts as an E3 enzyme (borrowing designations from the ubiquitin system) (41) and stimulates a second conjugation system, whereby Atg8 undergoes conversion from its free C-terminus state to its C-terminally lipidated form covalently modified by phosphatidylethanolamine (PE) (Fig.”
BackgroundOATL1, a novel autophagosome-resident Rab33B-GAP, regulates autophagosomal maturation
Itoh, T., Kanno, E., Uemura, T., Waguri, S., & Fukuda, M. (2011) · The Journal of Cell Biology · doi:10.1083/jcb.201008107 · Cited by 181
“The Atg12–5–16L1 complex interacts with Atg3, an E2 enzyme that catalyzes LC3 lipidation and facilitates the encounter between LC3 and PE on the membrane, like an E3 enzyme in the ubiquitin conjugation system (Hanada et al., 2007; Fujita et al., 2008a).”
Autophagy: molecular machinery, regulation, and implications for renal pathophysiology
Periyasamy‐Thandavan, S., Jiang, M., Schoenlein, P. V., & Dong, Z. (2009) · American Journal of Physiology-Renal Physiology · doi:10.1152/ajprenal.00033.2009 · Cited by 170
Autophagy Is Rapidly Induced by Salt Stress and Is Required for Salt Tolerance in Arabidopsis
Luo, L., Zhang, P., Zhu, R., Fu, J., Su, J., Zheng, J., Wang, Z., Wang, D., & Gong, Q. (2017) · Frontiers in Plant Science · doi:10.3389/fpls.2017.01459 · Cited by 173
“, 2000), and the ATG12-ATG5ATG16 complex as the E3 enzyme (Hanada et al., 2007).”
Liquidity Is a Critical Determinant for Selective Autophagy of Protein Condensates
Yamasaki, A., Alam, J. M., Noshiro, D., Hirata, E., Fujioka, Y., Suzuki, K., Ohsumi, Y., & Noda, N. N. (2020) · Molecular Cell · doi:10.1016/j.molcel.2019.12.026 · Cited by 174
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Autophagosome biogenesis comes out of the black box
Chang, C., Jensen, L. E., & Hurley, J. H. (2021) · Nature Cell Biology · doi:10.1038/s41556-021-00669-y · Cited by 178
Hepatitis C Virus Upregulates Beclin1 for Induction of Autophagy and Activates mTOR Signaling
Shrivastava, S., Bhanja Chowdhury, J., Steele, R., Ray, R., & Ray, R. B. (2012) · Journal of Virology · doi:10.1128/jvi.00616-12 · Cited by 163
“The third pathway that mediates autophagosome formation and elongation involves 2 ubiquitin-like conjugation processes that generate membrane-bound protein complexes (14, 19).”
Autophagy in tumor suppression and cancer therapy
Kung, C.-P., Budina, A., Balaburski, G. M., Bergenstock, M., & Murphy, M. E. (2011) · Critical Reviews in Eukaryotic Gene Expression · doi:10.1615/critreveukargeneexpr.v21.i1.50 · Cited by 168
Cleavage of Atg3 protein by caspase-8 regulates autophagy during receptor-activated cell death
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“The product of the first conjugation reaction, Atg12/Atg5 complex (together with Atg16), serves as an E3-like enzyme in LC3-PE conjugation [24].”
BackgroundThe Three Musketeers of Autophagy: phosphorylation, ubiquitylation and acetylation
McEwan, D. G., & Đikić, I. (2011) · Trends in Cell Biology · doi:10.1016/j.tcb.2010.12.006 · Cited by 168
“However, the Atg12–Atg5 conjugate forms a complex with Atg16 and this hierarchical assembly of proteins can drive the formation of Atg8–PE in an E3-like manner [32] (Figure 2a).”
BackgroundSong, Y., Zhang, S., Guo, X., Sun, K., Han, Z., Li, R., Zhao, Q., Deng, W.-J., Xie, X., zhang, J.-W., et al. (2013) · Cancer Letters · doi:10.1016/j.canlet.2013.07.021 · Cited by 162
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“the E2 in the Atg8 conjugation system and the Atg12–Atg5 complex acts as the E3 enzyme, bringing the Atg8-carrying E2-like enzyme, Atg3, in proximity to its substrate, the lipid phosphatidylethanolamine (PE) (Hanada et al., 2007).”
BackgroundKang, R., Loux, T., Tang, D., Schapiro, N. E., Vernon, P., Livesey, K. M., Krasinskas, A., Lotze, M. T., & Zeh, H. J. (2012) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1113865109 · Cited by 163
“The ATG12–ATG5 conjugate has an E3-like ubiquitin ligase activity-promoting protein lipidation in autophagy (18) that is critical for the elongation of the initiating autophagosomal membrane.”
BackgroundBORC coordinates encounter and fusion of lysosomes with autophagosomes
Jia, R., Guardia, C. M., Pu, J., Chen, Y., & Bonifacino, J. S. (2017) · Autophagy · doi:10.1080/15548627.2017.1343768 · Cited by 160
Structure of the Atg12–Atg5 conjugate reveals a platform for stimulating Atg8–PE conjugation
Noda, N. N., Fujioka, Y., Hanada, T., Ohsumi, Y., & Inagaki, F. (2012) · EMBO Reports · doi:10.1038/embor.2012.208 · Cited by 168
“Atg12 alone or the Atg5-Atg16 complex does not have E3-like activity for Atg8 lipidation, and conjugate formation between Atg12 and Atg5 is an essential step in this process [7,8]; therefore, it can be considered that Atg12 modification endows Atg5 with E3-like activity for Atg8 lipidation.”
Self-citationExtracellular matrix regulation of autophagy
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MIR181Aregulates starvation- and rapamycin-induced autophagy through targeting ofATG5
Tekirdağ, K. A., Korkmaz, G., Öztürk, D. G., Agami, R., & Gözüaçık, D. (2013) · Autophagy · doi:10.4161/auto.23117 · Cited by 161
“In addition to the activity of ATG7 (E1-like) and ATG3 (E2-like) enzymes, LC3-lipid conjugation requires the E3-like activity of ATG12–ATG5-ATG16L1 complex.(11) To”
BackgroundMai, S., Muster, B., Bereiter‐Hahn, J., & Jendrach, M. (2012) · Autophagy · doi:10.4161/auto.8.1.18174 · Cited by 162
“ATG5 forms a complex with ATG12 and ATG16L at the membrane of the evolving autophagosome.(13) The 18-kDa isoform LC3-I is localized in the cytosol and after conjugation to phosphatidylethanolamine the activated 16-kDa isoform LC3-II is situated within the autophagosomal membrane.”
BackgroundMBSJ MCC Young Scientist Award 2009 REVIEW: Selective autophagy regulates various cellular functions
Komatsu, M., & Ichimura, Y. (2010) · Genes to Cells · doi:10.1111/j.1365-2443.2010.01433.x · Cited by 163
“Subsequently, LC3-I conjugates to phosphatidylethanolamine (PE) (named LC3-II) through Atg7 (E1), Atg3 (E2) and Atg12–Atg5•Atg16 (E3), in a manner analogous to the ubiquitin-conjugation system (Ichimura et al. 2000; Kabeya et al. 2000; Hanada et al. 2007; Fujita et al. 2008b) (Fig.”
BackgroundSelf-citationThe elimination of accumulated and aggregated proteins: A role for aggrephagy in neurodegeneration
Yamamoto, A., & Simonsen, A. (2010) · Neurobiology of Disease · doi:10.1016/j.nbd.2010.08.015 · Cited by 155
Atg12–Atg5 conjugate enhances E2 activity of Atg3 by rearranging its catalytic site
Sakoh‐Nakatogawa, M., Matoba, K., Asai, E., Kirisako, H., Ishii, J., Noda, N. N., Inagaki, F., Nakatogawa, H., & Ohsumi, Y. (2013) · Nature Structural & Molecular Biology · doi:10.1038/nsmb.2527 · Cited by 162
Self-citationRegulation of autophagy by protein post-translational modification
Wani, W. Y., Boyer‐Guittaut, M., Dodson, M. B., Chatham, J. C., Darley-Usmar, V. M., & Zhang, J. (2014) · Laboratory Investigation · doi:10.1038/labinvest.2014.131 · Cited by 160
Autophagy is induced upon platelet activation and is essential for hemostasis and thrombosis
Ouseph, M. M., Huang, Y., Banerjee, M., Joshi, S., MacDonald, L. J., Zhong, Y., Liu, H., Li, X., Xiang, B., Zhang, G., et al. (2015) · Blood · doi:10.1182/blood-2014-09-598722 · Cited by 162
“One uses Atg7 and Atg10 (E1 and E2 enzymes, respectively) to form an Atg12–Atg5 conjugation.22-24 A second system uses Atg7, Atg3, and the Atg12–Atg5–Atg16L1 complex (E1, E2, and E3 enzymes, respectively) to catalyze the addition of phosphatidylethanolamine to the microtubule-associated protein 1A/B light chain 3 (LC3…”
MethodMitochondria and autophagy: Critical interplay between the two homeostats
Okamoto, K., & Kondo‐Okamoto, N. (2011) · Biochimica et Biophysica Acta (BBA) - General Subjects · doi:10.1016/j.bbagen.2011.08.001 · Cited by 155
AMPK-independent induction of autophagy by cytosolic Ca2+ increase
Grotemeier, A., Alers, S., Pfisterer, S. G., Paasch, F., Daubrawa, M., Dieterle, A., Viollet, B., Wesselborg, S., Proikas-Cezanne, T., & Stork, B. (2010) · Cellular Signalling · doi:10.1016/j.cellsig.2010.01.015 · Cited by 143
Autophagy: More Than a Nonselective Pathway
Reggiori, F., Komatsu, M., Finley, K. D., & Simonsen, A. (2012) · International Journal of Cell Biology · doi:10.1155/2012/219625 · Cited by 161
“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].”
BackgroundRegulation of autophagy: Modulation of the size and number of autophagosomes
Jin, M., & Klionsky, D. J. (2014) · FEBS Letters · doi:10.1016/j.febslet.2014.06.015 · Cited by 151
“The Atg12–Atg5–Atg16 complex may act as the E3 ligase for Atg8–PE conjugation [33], although it is not essential [34].”
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Disruption of Neuronal Autophagy by Infected Microglia Results in Neurodegeneration
Alirezaei, M., Kiosses, W. B., Flynn, C. T., Brady, N. R., & Fox, H. S. (2008) · PLoS ONE · doi:10.1371/journal.pone.0002906 · Cited by 151
“Similar to three dimensional imaging results (Figures 2 and 3), Western blot detection of LC3 revealed a time-dependent decrease in LC3-II levels, indicating that neuronal AV numbers were significantly decreased in the presence of the SIV-infected microglia supernatant in a time-dependent manner (Figure 4A).”
BackgroundInfluentialGao, M., Yeh, P.-Y., Lu, Y., Hsu, C., Chen, K., Lee, W.-C., Feng, W.-C., Chen, C., Kuo, M., & Cheng, A. (2008) · Cancer Research · doi:10.1158/0008-5472.can-08-1642 · Cited by 147
“ATG5 has been characterized as an ubiquitin-like protein involved in autophagosome formation ( 23 ), and a recent study has shown that OSU-03012 increases the expression of ATG5 and promotes ATG5-dependent formation of LC3 (24).”
BackgroundRole of melatonin in the regulation of autophagy and mitophagy: A review
Coto‐Montes, A. M., Boga, J. A., Rosales‐Corral, S., Fuentes‐Broto, L., Tan, D., & Reiter, R. J. (2012) · Molecular and Cellular Endocrinology · doi:10.1016/j.mce.2012.04.009 · Cited by 150
“PE is associated with both the phagophore and the autophagosomal membrane (Hanada et al., 2007; Fujita et al., 2008).”
ATG16L1: A multifunctional susceptibility factor in Crohn disease
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“This conjugate further recruits ATG16L1 (autophagy-related 16 like 1) to form a multimeric complex that can enhance the formation of MAP1LC3–PE conjugates [8,9].”
BackgroundObara, K., Noda, T., Niimi, K., & Ohsumi, Y. (2008) · Genes to Cells · doi:10.1111/j.1365-2443.2008.01188.x · Cited by 150
“Recent studies showed that the Atg12–Atg5 conjugate has an E3-like activity in Atg8-PE formation (Hanada et al. 2007; Fujita et al. 2008).”
BackgroundSelf-citationMitochondrial ROS and involvement of Bcl-2 as a mitochondrial ROS regulator
Chong, S. J. F., Low, I. C. C., & Pervaiz, S. (2014) · Mitochondrion · doi:10.1016/j.mito.2014.06.002 · Cited by 142
“Subsequently, the autophagosomal membrane elongation is facilitated by two ubiquitin-like conjugations; the conjugation of Atg12 to Atg5 and Atg8 to phosphoethanolamine (PE) (Fujita et al., 2008; Hanada et al., 2007; Scherz-Shouval and Elazar, 2011).”
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Self-citationHistory of the Selective Autophagy Research: How Did It Begin and Where Does It Stand Today?
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“During phagophore vesicle elongation, Atg12 is covalently conjugated to Atg5 in an ubiquitin-like manner (Mizushima et al., 1998; Hanada et al., 2007).”
BackgroundAutophagosome formation in mammalian cells
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“Interestingly, it has been shown that yeast Atg12-Atg5 stimulates the formation of Atg8-PE in vitro, and that Atg12-Atg5 can interact with Atg3 to enhance its activity [69].”
BackgroundAutophagy impairment in Parkinson’s disease
Karabiyik, C., Lee, M. J., & Rubinsztein, D. C. (2017) · Essays in Biochemistry · doi:10.1042/ebc20170023 · Cited by 141
“The transmembrane protein mATG9 may assist in the expansion of the phagophore by providing further lipids (14,15).”
BackgroundInnate, adaptive, and cell-autonomous immunity against Toxoplasma gondii infection
Sasai, M., & Yamamoto, M. (2019) · Experimental & Molecular Medicine · doi:10.1038/s12276-019-0353-9 · Cited by 154
Autophagy in plants: Physiological roles and post‐translational regulation
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“that AtATG12 and AtATG5 conjugates might also function in AtATG8–PE lipidation (Figure 1) (Hanada et al., 2007; Chung et al., 2010).”
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“Importantly, the ATG16L complex with ATG5– ATG12 has been demonstrated to serve as an E3 that promotes the lipidation of ATG8/LC3 [24, 25].”
Kreibich, S., Emmenlauer, M., Fredlund, J., Rämö, P., Münz, C., Dehio, C., Enninga, J., & Hardt, W. (2015) · Cell Host & Microbe · doi:10.1016/j.chom.2015.10.015 · Cited by 142
“ATG5, ATG12, and ATG16L1 form an E3-ubiquitin ligase of the ATG8-conjugation system involved in autophagosomeelongationandclosure (Fujita et al., 2008; Hanada et al., 2007; Mizushima et al., 2001, 2003).”
BackgroundLin, T., Chan, H.-H., Chen, S., Sarvagalla, S., Chen, P., Coumar, M. S., Cheng, S. M., Chang, Y.-C., Lin, C.-H., Leung, E. Y., et al. (2019) · Autophagy · doi:10.1080/15548627.2019.1671643 · Cited by 135
“ATG7 is a multi-role E1-like enzyme that facilitates LC3-lipidation, activates ATG12, and transfers the activated ATG12 to ATG10, which is an E2-like enzyme that facilitates the subsequent ATG12–ATG5 conjugation.”
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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