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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]
Citations
Cites
Hershko, A., & Ciechanover, A. (1998) · Annual Review of Biochemistry · doi:10.1146/annurev.biochem.67.1.425 · Cited by 8,840
Levine, B., & Klionsky, D. J. (2004) · Developmental Cell · doi:10.1016/s1534-5807(04)00099-1 · Cited by 3,728
Autophagy in Health and Disease: A Double-Edged Sword
Shintani, T., & Klionsky, D. J. (2004) · Science · doi:10.1126/science.1099993 · Cited by 2,559
A ubiquitin-like system mediates protein lipidation
Ichimura, Y., Kirisako, T., Takao, T., Satomi, Y., Shimonishi, Y., Ishihara, N., Mizushima, N., Tanida, I., Kominami, E., Ohsumi, M., et al. (2000) · Nature · doi:10.1038/35044114 · Cited by 2,139
Self-citationA protein conjugation system essential for autophagy
Mizushima, N., Noda, T., Yoshimori, T., Tanaka, Y., Ishii, T., George, M. D., Klionsky, D. J., Ohsumi, M., & Ohsumi, Y. (1998) · Nature · doi:10.1038/26506 · Cited by 1,758
Self-citationAutophagy: molecular machinery for self-eating
Yorimitsu, T., & Klionsky, D. J. (2005) · Cell Death and Differentiation · doi:10.1038/sj.cdd.4401765 · Cited by 1,566
Dissection of Autophagosome Formation Using Apg5-Deficient Mouse Embryonic Stem Cells
Mizushima, N., Yamamoto, A., Hatano, M., Kobayashi, Y., Kabeya, Y., Suzuki, K., Tokuhisa, T., Ohsumi, Y., & Yoshimori, T. (2001) · The Journal of Cell Biology · doi:10.1083/jcb.152.4.657 · Cited by 1,361
Self-citationMolecular dissection of autophagy: two ubiquitin-like systems
Ohsumi, Y. (2001) · Nature Reviews Molecular Cell Biology · doi:10.1038/35056522 · Cited by 1,240
Self-citationNakatogawa, H., Ichimura, Y., & Ohsumi, Y. (2007) · Cell · doi:10.1016/j.cell.2007.05.021 · Cited by 1,215
Self-citationSuzuki, K., Kirisako, T., Kamada, Y., Mizushima, N., Noda, T., & Ohsumi, Y. (2001) · The EMBO Journal · doi:10.1093/emboj/20.21.5971 · Cited by 1,060
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Low concentration of mercury induces autophagic cell death in rat hepatocytes
Chatterjee, S., Ray, A., Mukherjee, S., Agarwal, S., Kundu, R., & Bhattacharya, S. (2012) · Toxicology and Industrial Health · doi:10.1177/0748233712462442 · Cited by 28
“These two autophagic proteins are known to participate in elongation of the autophagosome membrane during vacuole formation (Hanada et al., 2007).”
BackgroundNew Roles of the Primary Cilium in Autophagy
Ávalos, Y., Peña‐Oyarzún, D., Budini, M., Morselli, E., & Criollo, A. (2017) · BioMed Research International · doi:10.1155/2017/4367019 · Cited by 32
“The incorporation of LC3 into autophagosomes is also mediated by the ATG5/ATG12 complex, which, together with ATG16L, forms a new complex that functions similarly to an E3 enzyme [54].”
BackgroundATG16 mediates the autophagic degradation of the 19S proteasomal subunits PSMD1 and PSMD2
Xiong, Q., Fischer, S., Karow, M. A., Müller, R., Meßling, S., & Eichinger, L. (2018) · European Journal of Cell Biology · doi:10.1016/j.ejcb.2018.09.002 · Cited by 28
Liang, J., Zhou, F., Xiong, X., Zhang, X., Li, S., Li, X., Gao, M., & Yu, W. H. (2019) · Aging · doi:10.18632/aging.102235 · Cited by 27
“The Atg12-Atg5-Atg16 complex forms during autophagosome formation, promoting autophagy [45, 46].”
BackgroundZhao, X., Feng, W., Zhu, X., Li, C., Ma, X., Li, X., Zhu, X., & Wei, D. (2019) · Frontiers in Microbiology · doi:10.3389/fmicb.2019.02690 · Cited by 27
“…system, Atg12 is catalyzed by Atg7 (E1 enzyme) and Atg10 (E2 enzyme) and then conjugated with Atg5 via an isomerized peptide bond with a lysine residue at the middle of Atg5 (Mizushima et al., 1998). the Atg12-Atg5 complex has an E3-like function in the lipidation of Atg8 (Hanada et al., 2007).”
BackgroundKuo, E. Y., Chang, H.-L., Lin, S., & Lee, T. (2020) · Frontiers in Plant Science · doi:10.3389/fpls.2020.00772 · Cited by 27
“…and its fusion with the lysosome/vacuolar membrane through the ubiquitinlike protein conjugation system (Ohsumi, 2001; Thompson and Vierstra, 2005; Hanada et al., 2007; Nakatogawa et al., 2007; Xie et al., 2008), which implies the implementation of a mature autophagosome and autolysosome…”
BackgroundAutophagy in skin barrier and immune‐related skin diseases
Liu, C., Gu, L., Ding, J., Meng, Q., Li, N., Dai, G., Li, Q., & Wu, X. (2021) · The Journal of Dermatology · doi:10.1111/1346-8138.16185 · Cited by 27
The crosstalk between sonodynamic therapy and autophagy in cancer
Zhang, Y., Zhao, Y., Zhang, Y., Liu, Q., Zhang, M., & Tu, K. (2022) · Frontiers in Pharmacology · doi:10.3389/fphar.2022.961725 · Cited by 28
“The ATG12–ATG5 conjugate binds ATG16L1 with a lysine residue (K) in ATG5 to form the ATG16L1 complex (Hanada et al., 2007).”
BackgroundThe Interplay of Autophagy and Oxidative Stress in the Kidney: What Do We Know?
Guo, H., & Bechtel‐Walz, W. (2023) · The Nephron journals/Nephron journals · doi:10.1159/000531290 · Cited by 31
Autophagy Suppression by Appendicitis and Appendectomy Protects Against Colitis
Cheluvappa, R., Luo, A. S., & Grimm, M. (2014) · Inflammatory Bowel Diseases · doi:10.1097/mib.0000000000000034 · Cited by 27
Marchantia polymorpha, a New Model Plant for Autophagy Studies
Norizuki, T., Kanazawa, T., Minamino, N., Tsukaya, H., & Ueda, T. (2019) · Frontiers in Plant Science · doi:10.3389/fpls.2019.00935 · Cited by 25
“This glycine is conjugated with phosphatidylethanolamine through the actions of E1-like Atg7, E2-like Atg3, and the E3like Atg12–Atg5–Atg16 complex (Ichimura et al., 2000; Hanada et al., 2007).”
BackgroundTindwa, H. J., Jo, Y. H., Patnaik, B. B., Lee, Y. S., Kang, S. S., & Han, Y. S. (2015) · Developmental & Comparative Immunology · doi:10.1016/j.dci.2015.02.017 · Cited by 26
“Neither Atg12 alone or Atg5-Atg16 conjugate have the E3-like enzyme activity, and thus, knockdown of Atg5 by RNAi would deplete the host organism of this ability to form the Atg12-Atg5-Atg16 complex and its stimulatory activity on the conversion of Atg8-I to Atg8-II (Fujioka et al., 2008; Hanada et al., 2007).”
BackgroundJin, S., Wei, J., You, L., Liu, H., & Qian, W. (2018) · Oncology Reports · doi:10.3892/or.2018.6370 · Cited by 27
Lee, H. I., Lee, J., Hwang, D., Lee, G., Kim, N., Kwon, M., Lee, H., Piao, D., Kim, H. J., Kim, N. Y., et al. (2019) · The FASEB Journal · doi:10.1096/fj.201900862r · Cited by 27
Fission Yeast Autophagy Machinery
Xu, D., & Du, L. (2022) · Cells · doi:10.3390/cells11071086 · Cited by 29
“Then, Atg7/ATG7, Atg3/ATG3, and the Atg12-Atg5/ATG12-ATG5 conjugate act as E1, E2, and E3 enzymes, respectively, to promote the conjugation of Atg8 to PE [42,117].”
BackgroundCrosstalk between mitophagy and innate immunity in viral infection
Fu, C., Cao, N., Liu, W., Zhang, Z., Yang, Z., Zhu, W., & Fan, S. (2022) · Frontiers in Microbiology · doi:10.3389/fmicb.2022.1064045 · Cited by 26
“Viruses are intracellular parasites without cellular structures, which target mitochondria in many ways to disrupt the homeostasis of mitochondria and in turn affect the metabolism and physiology of the host cell, promoting the replication and propagation of the virus itself in the host cell (Hanada et al., 2007).”
BackgroundNatural Compounds Targeting the Autophagy Pathway in the Treatment of Colorectal Cancer
Du, Y.-X., Mamun, A. A., Lü, A., & Zhang, H. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms24087310 · Cited by 25
“Another research group has reported that curcumin-induced autophagic cell death was activated through increased production of reactive oxygen species (ROS) in HCT116 human CRC cells, resulting in the accumulation of LC3-II and autophagosome development [144].”
BackgroundInfluentialSelective autophagy against membranous compartments
Pimentel‐Muiños, F. X., & Boada-Romero, E. (2014) · Autophagy · doi:10.4161/auto.27244 · Cited by 26
Levchenko, M., Lorenzi, I., & Dudek, J. (2016) · PLoS ONE · doi:10.1371/journal.pone.0168518 · Cited by 26
Effects of Fluoride on Autophagy in Mouse Sertoli Cells
Feng, Z., Liang, C., Manthari, R. K., Wang, C., & Zhang, J. (2018) · Biological Trace Element Research · doi:10.1007/s12011-018-1405-z · Cited by 26
Indirect estimation of the area density of Atg8 on the phagophore
Xie, Z., Nair, U., Geng, J., Szefler, M. B., Rothman, E. D., & Klionsky, D. J. (2009) · Autophagy · doi:10.4161/auto.5.2.7201 · Cited by 26
Transcription factors and cognate signalling cascades in the regulation of autophagy
Chandra, V., Bhagyaraj, E., Parkesh, R., & Gupta, P. (2016) · Biological Reviews · doi:10.1111/brv.12177 · Cited by 26
“The site of LC3 lipidation depends on membrane localization of the ATG16L complex, which functions as a scaffold for ATG8–PE conjugation (Hanada et al., 2007; Geng & Klionsky, 2008).”
BackgroundUbiquitin and Ubiquitin-like Modifiers in Plants
Park, H. J., Park, H. C., Lee, S. Y., Bohnert, H. J., & Yun, D. (2011) · Journal of Plant Biology · doi:10.1007/s12374-011-9168-5 · Cited by 25
“The ATG12-ATG5 conjugate, which promotes the formation of ATG8-PE conjugates, is a ubiquitin protein ligase E3-like enzyme that is essential for ATG8-mediated autophagy (Chung et al. 2010; Fujioka et al. 2008; Hanada et al. 2007).”
Cloherty, A. P. M., Rader, A. G., Compeer, B., & Ribeiro, C. M. S. (2021) · Viruses · doi:10.3390/v13020320 · Cited by 28
Endothelial Autophagy Dysregulation in Diabetes
Salemkour, Y., & Lenoir, O. (2023) · Cells · doi:10.3390/cells12060947 · Cited by 28
Bidirectional interplay between SARS-CoV-2 and autophagy
Zhou, H., Hu, Z., & Castro‐Gonzalez, S. (2023) · mBio · doi:10.1128/mbio.01020-23 · Cited by 27
Brickle, A., Tran, H., Lim, R., Liong, S., & Lappas, M. (2015) · Placenta · doi:10.1016/j.placenta.2015.10.015 · Cited by 25
The Activation and Function of Autophagy in Alcoholic Liver Disease
Khambu, B., Wang, L., Zhang, H., & Yin, X. (2017) · Current Molecular Pharmacology · doi:10.2174/1874467208666150817112654 · Cited by 27
“Notably, the Atg5-Atg12-Atg16 complex is required for the efficient conjugation of LC3 to PE, thus acting like an E3 ligase functionally [31].”
Cheung, Y.-T., Zhang, N. Q., Hung, C. H.-L., Lai, C. S.-W., Yu, M.-S., So, K., & Chang, R. C. (2010) · Journal of Cellular and Molecular Medicine · doi:10.1111/j.1582-4934.2009.00990.x · Cited by 25
“This suggests that ATG12 is involved in autophagosome maturation [38] through a transient process which is difficult to detect by immunocytochemical methods.”
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Alam, J., deHaro, D. L., Redding, K., Ré, R. N., & Cook, J. L. (2009) · Regulatory Peptides · doi:10.1016/j.regpep.2009.09.002 · Cited by 25
“In the final step, Apg8 is conjugated to membrane phosphoethanolamine by an E3-like activity that has not been fully characterized but may reside in a product of the second (Apg12) conjugation system [32].”
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“The recruitment of this intermediate at the phagophore permits the addition of PE by ATG3 with the help of the ATG5-12/16L1 complex, which acts as an E3 ubiquitin-like enzyme (5, 6).”
BackgroundAtg3 promotes Atg8 lipidation via altering lipid diffusion and rearrangement
Wang, S., Li, Y., & Ma, C. (2020) · Protein Science · doi:10.1002/pro.3866 · Cited by 24
“Atg7–Atg10 in pET11 vector and Atg12–Atg5 in pACYC184 vector were kindly gifts from Yoshinori Ohsumi.17 For in vivo imaging and Atg8 processing assay, Atg8 was cloned into pRS415 II vector (from add gene) with its native promoter and terminator and an EGFP fluorescent protein at the N-terminus.”
MethodFinetti, F., Cassioli, C., Cianfanelli, V., Zevolini, F., Onnis, A., Gesualdo, M., Brunetti, J., Cecconi, F., & Baldari, C. T. (2021) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2021.634003 · Cited by 24
“…0.0001 ATG16L1 is involved in determining the site of LC3 lipidation, functioning as a scaffold to recruit the ATG12-ATG5 conjugating enzyme and LC3 to allow for the transfer reaction of LC3 from ATG3 to phosphatidylethanolamine at the phagophore membrane (Fujita et al., 2008; Hanada et al., 2007).”
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Fischer, S., Rijal, R., Frommolt, P., Wagle, P., Konertz, R., Faix, J., Meßling, S., & Eichinger, L. (2019) · Cells · doi:10.3390/cells8010072 · Cited by 24
“Within the ATG12~5/16 complex, ATG16 is required for correct localization and the ATG12~5 conjugate possesses E3 ligase activity that promotes the conjugation of ATG8 to PE at the autophagic membrane [17,21,22].”
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Corkery, D., Wijayatunga, D., Feron, B. K. L., Herzog, L. K., Knyazeva, A., & Wu, Y. (2026) · The EMBO Journal · doi:10.1038/s44318-025-00672-1 · Cited by 24
The E3-ome gene-centric compendium reveals the human E3 ligase landscape
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BackgroundSun, L., Wang, X., Chen, L., Gao, Z., Xu, S., Chen, H., Fan, G., Wang, B., Feng, T., Wang, W., et al. (2023) · Cell Insight · doi:10.1016/j.cellin.2023.100127 · Cited by 23
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Self-citationcoordination, O., Elsasser, S., Elia, L. P., Morimoto, R. I., Powers, E. T., Elsasser, S., Finley, D. J., Costa, B., Budron, M., Tokuno, Z., et al. (2023) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2023.03.22.533675 · Cited by 32
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“The ATG12–ATG5-ATG16L1 pathway starts with the ubiquitin-like protein ATG12, conjugated to ATG5 through a series of enzymatic steps involving ATG7 (an E1-like enzyme) and ATG10 (an E2-like enzyme) [65].”
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BackgroundKang, S., Tak, J.-H., Cho, J.-H., Lee, H.-J., & Jung, Y. (2010) · Genes & Genomics · doi:10.1007/s13258-010-0139-x · Cited by 21
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“It has been suggested that the ATG5– ATG12–ATG16L1 protein complex is able to catalyze the lipidation of ATG8/LC3, suggesting an interplay between these apparently distinct pathways [2,3].”
BackgroundMatthias, J., Meßling, S., & Eichinger, L. (2015) · European Journal of Cell Biology · doi:10.1016/j.ejcb.2015.10.007 · Cited by 22
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Xie, Z., Nair, U., & Klionsky, D. J. (2008) · Autophagy · doi:10.4161/auto.6692 · Cited by 22
Alfy-dependent elimination of aggregated proteins by macroautophagy
Yamamoto, A., & Simonsen, A. (2011) · Autophagy · doi:10.4161/auto.7.3.14234 · Cited by 21
Demine, S., Tejerina, S., Bihin, B., Thiry, M., Reddy, N., Renard, P., Raes, M., Jadot, M., & Arnould, T. (2018) · Journal of Cellular Physiology · doi:10.1002/jcp.25994 · Cited by 21
“autophagosome formation (Hanada et al., 2007; Komatsu et al., 2005; Tanida, Tanida-Miyake, Ueno, & Kominami, 2001), we next studied the effect of Atg5 and/or Atg7 silencing on the glycerol”
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“1) [71, 72].”
Modulation of Autophagy: A Novel “Rejuvenation” Strategy for the Aging Liver
Xu, F., Tautenhahn, H., Dirsch, O., & Dahmen, U. (2021) · Oxidative Medicine and Cellular Longevity · doi:10.1155/2021/6611126 · Cited by 21
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Zheng, X., Wang, W., Liu, R., Huang, H., Zhang, R., & Sun, L. (2012) · Europe PMC (PubMed Central) · doi:10.3969/j.issn.1673-5374.2012.17.004 · Cited by 21
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Tezil, T., & Başağa, H. (2014) · Current Pharmaceutical Design · doi:10.2174/13816128113196660702 · Cited by 21
Li, X., Li, Y., Fang, S., et al. (2017) · Antiviral Research · doi:10.1016/j.antiviral.2017.01.016 · Cited by 21
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HIF1α promotes prostate cancer progression by increasing ATG5 expression
Yu, K., Xiang, L., Li, S., Wang, S., Chen, C., & Mu, H. (2019) · Animal Cells and Systems · doi:10.1080/19768354.2019.1658637 · Cited by 21
“systems, the ATG5-ATG12 conjugate and LC3-ATG8 conjugate, which are essential for the autophagosome formation (Hanada et al. 2007; Weidberg, Shpilka, et al. 2011).”
BackgroundSyntaxin 16’s Newly Deciphered Roles in Autophagy
Tang, B. L. (2019) · Cells · doi:10.3390/cells8121655 · Cited by 21
“LC3 is first processed at its C terminus by the cysteine peptidase Atg4 to LC3-I, with the latter subsequently conjugated with PE to LC3-II by the E3-like Atg16/Atg16L–Atg5 complex [43].”
BackgroundFunctional Characterisation of the Autophagy ATG12~5/16 Complex in Dictyostelium discoideum
Karow, M. A., Fischer, S., Meßling, S., Konertz, R., Riehl, J., Xiong, Q., Rijal, R., Wagle, P., Clemen, C. S., & Eichinger, L. (2020) · Cells · doi:10.3390/cells9051179 · Cited by 22
“ATG5, ATG12 and ATG16 act in canonical autophagy together as a heterohexameric complex, which provides the E3-like ligase activity for conjugation of ATG8 to PE [17].”
BackgroundThe Role of WIPI2, ATG16L1 and ATG12-ATG5 in Selective and Nonselective Autophagy
Campisi, D., Hawkins, N., Bonjour, K., & Wollert, T. (2025) · Journal of Molecular Biology · doi:10.1016/j.jmb.2025.169138 · Cited by 22
Yu, L., Sun, R., Xu, K., Pu, Y., Huang, J., Liu, M., Chen, M., Zhang, J., Yin, L., & Pu, Y. (2021) · Toxicology Research · doi:10.1093/toxres/tfab053 · Cited by 21
Merkley, S. D., Goodfellow, S. M., Guo, Y. P., Wilton, Z. E. R., Byrum, J. R., Schwalm, K. C., Dinwiddie, D. L., Gullapalli, R. R., Deretic, V. P., Hernández, A. J., et al. (2021) · Journal of Crohn s and Colitis · doi:10.1093/ecco-jcc/jjab144 · Cited by 20
In vitro systems for Atg8 lipidation
Zens, B., Sawa-Makarska, J. Z., & Martens, S. (2014) · Methods · doi:10.1016/j.ymeth.2014.11.004 · Cited by 20
3-Methyladenine blocks Toxoplasma gondii division prior to centrosome replication
Wang, Y., Karnataki, A., Parsons, M., Weiss, L. M., & Orlofsky, A. (2010) · Molecular and Biochemical Parasitology · doi:10.1016/j.molbiopara.2010.05.020 · Cited by 20
“Macroautophagy requires the presence of Atg5, which functions as part of a ubiquitin-like conjugation system that results in the conversion of LC3 (Atg8) to a lipidated form (LC3-II) that associates with the developing autophagosome [21].”
BackgroundYamamoto, H., Shima, T., Yamaguchi, M., et al. (2015) · Journal of Biological Chemistry · doi:10.1074/jbc.m115.684233 · Cited by 20
Self-citationTazarotene-Induced Gene 1 Enhanced Cervical CellAutophagy through Transmembrane Protein 192
Shyu, R., Wang, C., Wu, C., Chen, M., Lee, M., Wang, L., Jiang, S., & Tsai, F. (2016) · Molecules and Cells · doi:10.14348/molcells.2016.0161 · Cited by 20
“Many Atg genes are involved in autophagosome formation, including the well-known Atg12-Atg5 and Atg8 (micro-tubule-associated protein 1 light chain 3, LC3)-phosphatidyle- thanolamine systems (Dooley et al., 2014; Hanada et al., 2007).”
A New Linkage between the Tumor Suppressor RKIP and Autophagy: Targeted Therapeutics
Wang, Y., & Bonavida, B. (2018) · Critical Reviews™ in Oncogenesis · doi:10.1615/critrevoncog.2018027211 · Cited by 19
Alcohol-induced autophagy via upregulation of PIASy promotes HCV replication in human hepatoma cells
Ran, M., Chen, H., Liang, B., Liao, W., Jiang, J., Huang, J., Ning, C., Zang, N., Zhou, B., Liao, Y., et al. (2018) · Cell Death and Disease · doi:10.1038/s41419-018-0845-x · Cited by 20
Oleic acid-induced defective autolysosome shows impaired lipid degradation
Lee, D.-H., Ahn, J., Jang, Y. J., Ha, T. Y., & Jung, C. H. (2019) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2019.04.040 · Cited by 20
Role of Autophagy in Male Reproductive Processes in Land Plants
Norizuki, T., Minamino, N., & Ueda, T. (2020) · Frontiers in Plant Science · doi:10.3389/fpls.2020.00756 · Cited by 20
Serramito-Gómez, I., Boada-Romero, E., Villamuera, R., Fernández-Cabrera, Á., Cedillo, J. L., Martín‐Regalado, Á., Carding, S. R., Mayer, U., Powell, P. P., Wileman, T. E., et al. (2020) · Nature Communications · doi:10.1038/s41467-020-19670-4 · Cited by 22
Xie, W., Xue, Y., Song, X., Zhang, H., Chang, G., & Shen, X.-Z. (2022) · Journal of Dairy Science · doi:10.3168/jds.2022-22252 · Cited by 17
Tang, X., Deng, P., Jiang, Y., Zhang, L., He, Y., & Yang, H. (2023) · Biomedicines · doi:10.3390/biomedicines11112878 · Cited by 19
“I ratio and the formation of Atg12-Atg5 conjugation are critical for the formation of autophagosome [83].”
BackgroundMechanisms of autophagy and pexophagy in yeasts
Sibirny, A. А. (2011) · Biochemistry (Moscow) · doi:10.1134/s0006297911120017 · Cited by 19
Autophagy in herpesvirus immune control and immune escape
Taylor, G. S., Mautner, J., & Münz, C. (2011) · Herpesviridae · doi:10.1186/2042-4280-2-2 · Cited by 18
“5 (HSV) Figure 1 Immune escape from innate restriction and viral antigen presentation of herpesviruses by macroautophagy. a-, b- and g-herpesviruses (herpes simplex virus [HSV], human cytomegalovirus [HCMV], Kaposi sarcoma associated herpesvirus [KSHV], herpesvirus saimiri [HVS] and murine herpesvirus 68 [MHV68]) inhi…”
BackgroundInfluentialEndoplasmic Reticulum Stress and Autophagy
Kabir, M. F., Kim, H., & Chae, H. (2019) · IntechOpen eBooks · doi:10.5772/intechopen.81381 · Cited by 21
Autophagy in the control and pathogenesis of parasitic infections
Ghartey‐Kwansah, G., Adu‐Nti, F., Aboagye, B., Ankobil, A., Essuman, E. E., Opoku, Y. K., Abokyi, S., Abu, E. K., & Boampong, J. N. (2020) · Cell & Bioscience · doi:10.1186/s13578-020-00464-6 · Cited by 20
Escaping the Lion’s Den: redirecting autophagy for unconventional release and spread of viruses
Teo, Q. W., van Leur, S. W., & Sanyal, S. (2020) · FEBS Journal · doi:10.1111/febs.15590 · Cited by 18
Lipidation of Atg8: How is substrate specificity determined without a canonical E3 enzyme?
Nakatogawa, H., Oh‐oka, K., & Ohsumi, Y. (2008) · Autophagy · doi:10.4161/auto.6646 · Cited by 19
Self-citationAutophagy in Viral Development and Progression of Cancer
Suares, A., Medina, M. V., & Coso, O. A. (2021) · Frontiers in Oncology · doi:10.3389/fonc.2021.603224 · Cited by 19
Ma, Y., Jiao, Z., Liu, X., Zhang, Q., Piao, C., Xu, J., & Wang, H. (2022) · Stem Cell Research & Therapy · doi:10.1186/s13287-022-03109-2 · Cited by 19
“In ubiquitinbinding reactions, the ATG5-ATG12 complex promotes the formation of ATG8-PE in a manner similar to the function of E3 enzymes [38].”
BackgroundNakamura, S., Nakamura, K., Yokoi, Y., Shimizu, Y., Ohira, S., Hagiwara, M., Song, Z., Gan, L. H., Aizawa, T., Hashimoto, D., et al. (2023) · Scientific Reports · doi:10.1038/s41598-023-30997-y · Cited by 18
Plant reoviruses hijack autophagy in insect vectors
Liú, W., Wèi, T., & Wang, X. (2023) · Trends in Microbiology · doi:10.1016/j.tim.2023.06.008 · Cited by 20
Hypothalamic lipophagy and energetic balance
Singh, R. (2011) · Aging · doi:10.18632/aging.100393 · Cited by 19
“The elongation of the limiting membrane and autophagosome formation requires two independent conjugation cascades occurring in parallel, the Atg5/12 and the light chain-3 (LC3, Atg8 in yeast) cascades [24-26], both of which require a number of additional Atg proteins including the crucial ubiquitin E1-like ligase, Atg…”
BackgroundLi, Y.-B., Yang, T., Wang, J., & Zhao, X. (2018) · Frontiers in Endocrinology · doi:10.3389/fendo.2018.00028 · Cited by 18
“The complex functions as an ubiquitin–protein ligase (E3)-like enzyme to transfer microtubule-associated protein 1A/1B-light chain 3 (LC3 in mammals, also known as ATG8 in yeast) from ATG3 to phosphatidylethanolamine (PE) by stimulating the E2 activity of ATG3 (7).”
BackgroundRegulation of inner nuclear membrane associated protein degradation
Koch, B. A., & Yu, H.-G. (2019) · Nucleus · doi:10.1080/19491034.2019.1644593 · Cited by 16
“This conjugates then binds Atg16 to form an E3-like complex that stimulates the conjugation of Atg8 to the lipid phosphatidylethanolamine (PE, Atg8-PE) [85,86].”
BackgroundLi, C., Wang, L., Zhang, X., Wei, J., & Qin, Q. (2019) · Fish & Shellfish Immunology · doi:10.1016/j.fsi.2019.09.004 · Cited by 18
Degradation of the Tumor Suppressor PDCD4 Is Impaired by the Suppression of p62/SQSTM1 and Autophagy
Manirujjaman, M., Ozaki, I., Murata, Y., Guo, J. H., Xia, J., Nishioka, K., Perveen, R., Takahashi, H., Anzai, K., & Matsuhashi, S. (2020) · Cells · doi:10.3390/cells9010218 · Cited by 19
“ATG5-ATG12 conjugates work like E-3 ligase to conjugate LC3-I to lipid phosphatidyl ethanolamine (PE) and thereby form LC3-II in the growing autophagosome membrane [53,54].”
BackgroundStefaniak, S., Wojtyla, Ł., Pietrowska‐Borek, M., & Borek, S. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21062205 · Cited by 19
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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