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.
Overview
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
In the citing paper
“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
Self-citation
Flagged first, then by citations
Cited by
Sorted by citations
Items 501–600 of 1,000
The interplay between oxidative stress and autophagy in chronic obstructive pulmonary disease
Zhao, X., Zhang, Q., & Zheng, R. (2022) · Frontiers in Physiology · doi:10.3389/fphys.2022.1004275 · Cited by 48
“Moreover, the recruitment of LC3-II to autophagosomes is mediated by the ATG5-ATG12-ATG16L complex, which also contributes to the coupling with LC3 (Hanada et al., 2007).”
BackgroundZhang, L., Liú, W., Wu, N., Wang, H., Zhang, Z., Liu, Y., & Wang, X. (2023) · PLoS Pathogens · doi:10.1371/journal.ppat.1011134 · Cited by 42
“The appearance of Atg8-II marks the activation of autophagy pathways [17].”
BackgroundInfluentialPhosphoinositide‐binding proteins in autophagy
Lystad, A. H., & Simonsen, A. (2016) · FEBS Letters · doi:10.1002/1873-3468.12286 · Cited by 43
Zhao, E., Tang, C., Jiang, X., Weng, X., Zhong, X., Zhang, D., Hou, J., Wang, F., Huang, M., & Cui, H. (2017) · Cellular Signalling · doi:10.1016/j.cellsig.2017.05.011 · Cited by 41
Human ATG3 binding to lipid bilayers: role of lipid geometry, and electric charge
Hervás, J. H., Landajuela, A., Antón, Z., Shnyrova, A. V., Goñi, F. M., & Alonso, A. (2017) · Scientific Reports · doi:10.1038/s41598-017-15057-6 · Cited by 41
Structure and potential function of γ‐aminobutyrate type A receptor‐associated protein
Mohrlüder, J., Schwarten, M., & Willbold, D. (2009) · FEBS Journal · doi:10.1111/j.1742-4658.2009.07207.x · Cited by 45
Molecular basis of canonical and bactericidal autophagy
Noda, T., & Yoshimori, T. (2009) · International Immunology · doi:10.1093/intimm/dxp088 · Cited by 42
“(iv) A yeast Atg12‐Atg5 conjugate facilitates the Atg8 lipidation reaction in vitro ( 31 ).”
BackgroundKhater, S. I., Almanaa, T. N., Fattah, D. M. A., Khamis, T., Seif, M. M., Dahran, N. A., Alqahtani, L. S., Metwally, M. M. M., Mostafa, M., Albedair, R. A., et al. (2023) · Antioxidants · doi:10.3390/antiox12061220 · Cited by 40
“Moreover, there was upregulation in the expression pattern of LC3-II, a marker of autophagy [55], which was decreased in the diabetic group but was significantly (p < 0.”
BackgroundIvancevic, A. M., Simpson, D. M., Joyner, O., Bagby, S. M., Nguyen, L. L., Bitler, B. G., Pitts, T. M., & Chuong, E. B. (2024) · Science Advances · doi:10.1126/sciadv.ado1218 · Cited by 42
Contribution of autophagy to antiviral immunity
Rey-Jurado, E., Riedel, C. A., González, P. A., Bueno, S. M., & Kalergis, A. M. (2015) · FEBS Letters · doi:10.1016/j.febslet.2015.07.047 · Cited by 40
“Subsequently, autophagosome formation is catalyzed by two ubiquitin-like conjugation systems: the Atg12-Atg5-ATG16L and Atg4B-Atg3-Atg7 complexes [27,28].”
BackgroundBrennand, A., Rico, E., & Michels, P. A. M. (2012) · Cells · doi:10.3390/cells1030346 · Cited by 41
“The ATG12-ATG5-ATG16 complex seems to serve as an E3-like protein and increases the rate of the association of ATG8 to the membrane [51].”
BackgroundAtg21 organizes Atg8 lipidation at the contact of the vacuole with the phagophore
Munzel, L., Neumann, P., Otto, F. B., et al. (2020) · Autophagy · doi:10.1080/15548627.2020.1766332 · Cited by 40
PKD2/polycystin-2 induces autophagy by forming a complex with BECN1
Peña‐Oyarzún, D., Rodriguez–Peña, M., Burgos‐Bravo, F., Vergara, A., Kretschmar, C., Sotomayor-Flores, C., Ramírez‐Sarmiento, C. A., SMEDT, H. D., Reyes, M., Perez, W., et al. (2020) · Autophagy · doi:10.1080/15548627.2020.1782035 · Cited by 42
“Ranaghan, from Broad Institute of MIT and Harvard University, USA, for providing the BECN1[1-265]- and the BECN1[248-450]-coding plasmids; Dr.”
BackgroundThe twoC. elegansATG-16 homologs have partially redundant functions in the basal autophagy pathway
Zhang, H., Wu, F., Wang, X., Du, H., Wang, X., & Zhang, H. (2013) · Autophagy · doi:10.4161/auto.26095 · Cited by 39
Álvarez, V. E., Kosec, G., Sant'Anna, C., Türk, V., Cazzulo, J. J., & Turk, B. (2008) · Autophagy · doi:10.4161/auto.5592 · Cited by 40
Schreiber, A., Collins, B. C., Davis, C. T., Enchev, R. I., Sedra, A., D’Antuono, R., Aebersold, R. H., & Peter, M. (2021) · Molecular Cell · doi:10.1016/j.molcel.2021.10.024 · Cited by 39
“The Atg5-Atg16 complex is not active as E3 unless conjugated to Atg12 (Hanada et al., 2007; Metlagel et al., 2013).”
BackgroundButton, R. W., Vincent, J. H., Strang, C. J., & Luo, S. (2016) · Oncotarget · doi:10.18632/oncotarget.6986 · Cited by 41
“The Atg5-12 conjugate (Atg5-12) is an E3 ligase to catalyse LC3-PE (LC3-II) conjugation that also requires E1-like Atg7 and E2-like Atg3 [9-11].”
BackgroundLi, S.-P. (2016) · World Journal of Gastroenterology · doi:10.3748/wjg.v22.i18.4501 · Cited by 37
Pillich, H., Puri, M., & Chakraborty, T. (2016) · Current topics in microbiology and immunology · doi:10.1007/82_2016_30 · Cited by 42
An, J., Zhou, Q., Wu, M., Wang, L., Zhong, Y., Feng, J., Shang, Y., & Chen, Y. (2018) · Toxicology in Vitro · doi:10.1016/j.tiv.2018.09.008 · Cited by 39
“This triplet complex facilitates conjugation of ubiquitin-like LC3 to lipid phosphatidylethanolamine through the E1-like enzyme ATG7 and E2-like enzyme ATG3 to expand the autophagophore (Hanada et al., 2007; Tanida et al., 2002).”
BackgroundThe role of lipids in autophagy and its implication in neurodegeneration
Hernández-Díaz, S., & Soukup, S. (2020) · Cell Stress · doi:10.15698/cst2020.07.225 · Cited by 39
“ATG8 is then transferred to the E2 equivalent ATG3 prior to the conjugation of the PE that is carried by the ATG5-ATG12 complex acting as an E3 ligase [70, 73].”
BackgroundMagrì, A., Lipari, C. L. R., Risiglione, P., Zimbone, S., Guarino, F., Caccamo, A., & Messina, A. A. (2023) · Cell Death and Disease · doi:10.1038/s41419-023-05643-0 · Cited by 40
“To assess whether the increase in TSPO expression affected mitophagy, we measured the protein levels of the autophagy marker Atg12, which represents one of the fundamental components of the autophagosome [45].”
BackgroundAUTOPHAGY IN PLASMODIUM , A MULTIFUNCTIONAL PATHWAY?
Hain, A. U. P., & Bosch, J. (2013) · Computational and Structural Biotechnology Journal · doi:10.5936/csbj.201308002 · Cited by 39
Autophagy in cerebral ischemia and the effects of traditional Chinese medicine
Xiao-ping, H., Ding, H., Lu, J.-D., Tang, Y., Bing-xiang, D., & Deng, C.-Q. (2015) · Journal of Chinese Integrative Medicine · doi:10.1016/s2095-4964(15)60187-x · Cited by 38
The Neuron-Specific Protein TMEM59L Mediates Oxidative Stress-Induced Cell Death
Zheng, Q., Zheng, X., Zhang, L., Luo, H., Qian, L., Fu, X., Liu, Y., Gao, Y., Niu, M., Meng, J., et al. (2016) · Molecular Neurobiology · doi:10.1007/s12035-016-9997-9 · Cited by 38
“then acts as an E3 ligase to conjugate LC3-I to phosphatidylethanolamine (PE) [8].”
The role of autophagy in the pathogenesis of systemic lupus erythematosus
Liu, X., Qin, H., & Xu, J. (2016) · International Immunopharmacology · doi:10.1016/j.intimp.2016.09.017 · Cited by 39
Lai, C., Huang, J.-C., Cheng, H., et al. (2018) · Cellular Microbiology · doi:10.1111/cmi.12947 · Cited by 38
“component for LC3 lipidation and autophagosome formation (Hanada et al., 2007).”
BackgroundEssential role of autophagy in resource allocation during sexual reproduction
Gao, H., Khawar, M. B., & Li, W. (2019) · Autophagy · doi:10.1080/15548627.2019.1628543 · Cited by 38
Bae, J., Jang, Y., Kim, H., Mahato, K., Schaecher, C., Kim, I. M., Kim, E., & Ro, S. (2019) · Scientific Reports · doi:10.1038/s41598-019-50965-9 · Cited by 38
Retromer regulates the lysosomal clearance of MAPT/tau
Carosi, J. M., Hein, L. K., van den Hurk, M., Adams, R., Milky, B., Singh, S., Bardy, C., Denton, D., Kumar, S., & Sargeant, T. J. (2020) · Autophagy · doi:10.1080/15548627.2020.1821545 · Cited by 41
Liu, P., Farooqı, A. A., Peng, S., Yu, T., Dahms, H.-U., Lee, C., Tang, J., Wang, S.-C., Shu, C., & Chang, H. (2020) · Seminars in Cancer Biology · doi:10.1016/j.semcancer.2020.10.009 · Cited by 38
Involvement of PRRSV NSP3 and NSP5 in the autophagy process
Zhang, W., Chen, K., Guo, Y., et al. (2019) · Virology Journal · doi:10.1186/s12985-019-1116-x · Cited by 37
“In this process, two proteins, namely, ATG12 and ATG5, form complexes via ubiquitin-like conjugation [11, 12] .”
BackgroundHill, C. N., Hernández‐Cáceres, M. P., Asencio, C., Torres, B. M., Solis, B., & Owen, G. I. (2020) · Frontiers in Oncology · doi:10.3389/fonc.2020.605314 · Cited by 38
“Subsequently, ATG7 and ATG3 activity enable LC3-I conjugation to the lipid PE to form LC3-II, which is then recruited to the inner and outer surface of the autophagosome in an ATG5-ATG12 dependent manner (59).”
BackgroundLi, X., Yan, Y., Zhou, X., Huang, C., & Wu, M. (2014) · The Journal of Immunology · doi:10.4049/jimmunol.1401958 · Cited by 37
“Atg7, an E1-like ubiquitin, is a critical factor for the formation of an Atg12-Atg5-Atg16L1 complex (5) and has been recently shown critical for immune response against bacterial infections (6–8).”
BackgroundAutophagy as a target for hematological malignancy therapy
Dong, Z., Liang, S., Hu, J., Jin, W., Zhan, Q., & Zhao, K. (2016) · Blood Reviews · doi:10.1016/j.blre.2016.04.005 · Cited by 37
Ryabovol, V., & Minibayeva, F. V. (2016) · Biochemistry (Moscow) · doi:10.1134/s0006297916040052 · Cited by 37
“It has been shown that the ATG12–ATG5 complex inter acts with ATG3 in vitro and promotes ATG8 transfer from ATG3 to PE [59].”
BackgroundWang, Y., Wen, X., Hao, D., Zhou, M., Li, X., He, G., & Jiang, X. L. (2019) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2019.108775 · Cited by 37
Selenotranscriptome Network in Non-alcoholic Fatty Liver Disease
Day, K., Seale, L. A., Graham, R. M., & Cardoso, B. R. (2021) · Frontiers in Nutrition · doi:10.3389/fnut.2021.744825 · Cited by 38
“These proteins participate in a ubiquitin-like pathway which is a precursor to phagophore formation (75).”
Atg8–PE protein-based in vitro biochemical approaches to autophagy studies
Huang, X. S., Yao, J., Liu, L., Luo, Y., & Yang, A. (2022) · Autophagy · doi:10.1080/15548627.2022.2025572 · Cited by 37
“Finally, the PE-modified peptide is ligated with MBP-LC3B[1-114] MESNa thioester under folding conditions in the presence of the detergent β-octylglucoside, with 4-mercaptophenylacetic acid (MPAA) serving as a catalyst.”
BackgroundMethodInfluentialAutophagy in toxicology: self‐consumption in times of stress and plenty
Bolt, A. M., & Klimecki, W. T. (2012) · Journal of Applied Toxicology · doi:10.1002/jat.1787 · Cited by 36
“Atg8 is conjugated to the target lipid PE, facilitated by the E3-like Atg12–Atg5 conjugate, and then attaches to both the inner and outer membranes of the phagophore (Hanada et al., 2007).”
BackgroundDever, S. M., Rodriguez, M., Lapierre, J., Costin, B. N., & El‐Hage, N. (2015) · Frontiers in Microbiology · doi:10.3389/fmicb.2015.00653 · Cited by 36
“ATG7 acts as an E1-like enzyme involved in formation of the ATG12–ATG5 conjugate (Tanida et al., 2001, 2012), which then acts as an E3-like enzyme in the LC3 lipidation reaction (Hanada et al., 2007).”
BackgroundHalder, P., Datta, C., Kumar, R., Sharma, A. K., Basu, J., & Kundu, M. (2014) · Cellular Microbiology · doi:10.1111/cmi.12396 · Cited by 39
“Two ubiquitin-like conjugation systems ATG12–ATG16 (Suzuki et al., 2001; Hanada et al., 2007) and ATG8 (or MAP1LC3B)–phosphatidylethanolamine are recruited to the phagophore that elongates to form the autophagosome containing encapsulated cytoplasmic material (Mizushima et al., 1998; 2011).”
BackgroundInfluentialXiong, Q., Ünal, C., Matthias, J., Steinert, M., & Eichinger, L. (2015) · Open Biology · doi:10.1098/rsob.150008 · Cited by 36
“In this tetrameric complex, ATG16 determines the binding site at the preautophagosomal structure (PAS) in yeast or the isolation membrane in higher eukaryotes [10,14], while ATG12–ATG5 catalyses the lipidation of ATG8 with phosphatidylethanolamine (PE) through its E3-ligase activity [15].”
BackgroundModulation of translation and induction of autophagy by bacterial exoproducts
von Hoven, G., Kloft, N., Neukirch, C., Ebinger, S., Bobkiewicz, W., Weis, S., Böller, K., Janda, K. D., & Husmann, M. (2012) · Medical Microbiology and Immunology · doi:10.1007/s00430-012-0271-0 · Cited by 36
“In the case of LC3 addition of PE is catalyzed by Atg7, Atg3 and Atg12/ Atg5-conjugate, which function as E1-like, E2-like and E3-like enzymes, respectively [13, 14].”
Carvajal, L., Gutiérrez, J., Morselli, E., & Leiva, A. (2021) · Frontiers in Oncology · doi:10.3389/fonc.2021.637594 · Cited by 39
“The ATG5–ATG12 complex then interacts with ATG16L, forming a new complex that works like an E3 enzyme, assisting the incorporation of LC3-II into the membrane of the phagophore (153).”
BackgroundThe Interplay of HIV and Autophagy in Early Infection
Cabrera-Rodríguez, R., Pérez-Yanes, S., Estévez‐Herrera, J., Márquez-Arce, D., Cabrera, C., Espert, L., Blanco, J., & Valenzuela-Fernández, A. (2021) · Frontiers in Microbiology · doi:10.3389/fmicb.2021.661446 · Cited by 37
The Interplay Between Autophagy and Regulated Necrosis
Zhang, L., Cui, T., & Wang, X. (2022) · Antioxidants and Redox Signaling · doi:10.1089/ars.2022.0110 · Cited by 39
“The ATG12-ATG5-ATG16 complex mediates the recruitment and conversion of microtubule-associated protein 1 light chain 3 (LC3) from LC3-I to its lipidated form, LC3-II (marker of autophagy) (Hanada et al, 2007).”
Structural view on autophagosome formation
Noda, N. N. (2023) · FEBS Letters · doi:10.1002/1873-3468.14742 · Cited by 40
“In contrast, Atg3 requires E3 for mediating the conjugation reaction between Atg8 and PE in cells, although Atg3 can facilitate Atg8 – PE formation without E3 in vitro when using liposomes with non-physiologically high PE content [24,65].”
BackgroundSelf-citationPhospholipids in Autophagosome Formation and Fusion
Martens, S., Nakamura, S., & Yoshimori, T. (2016) · Journal of Molecular Biology · doi:10.1016/j.jmb.2016.10.029 · Cited by 37
“WIP2 was also shown to recruit the ATG12–ATG5-ATG16L1 complex to the isolation membrane, thus linking PI3P to the ATG8 conjugation machinery [66, 67].”
BackgroundInfluentialProtein Kinase C Isozymes and Autophagy during Neurodegenerative Disease Progression
Kaleli, H. N., Ozer, E., Kaya, V. O., & Kutlu, Ö. (2020) · Cells · doi:10.3390/cells9030553 · Cited by 36
“Here, the ATG7 and ATG10 proteins, which regulate the addition of ATG12 in a manner similar to ubiquitination, play the E1 and E2-like role, respectively [51].”
BackgroundOld and New Concepts in Ubiquitin and NEDD8 Recognition
Santonico, E. (2020) · Biomolecules · doi:10.3390/biom10040566 · Cited by 36
“As an example, ATG12 is solely conjugated to ATG3 and ATG5 [68,69] and together with ATG8, the only Ubl that is conjugated to phospholipids [56] they are involved in autophagy.”
BackgroundTGF -activated kinase 1 (TAK1)-binding proteins (TAB) 2 and 3 negatively regulate autophagy
Takaesu, G., Kobayashi, T., & Yoshimura, A. (2011) · The Journal of Biochemistry · doi:10.1093/jb/mvr123 · Cited by 37
Targeting Autophagy for Developing New Therapeutic Strategy in Intervertebral Disc Degeneration
Bahar, M. E., Hwang, J. S., Ahmed, M., Lai, T. H., Pham, T. M., Elashkar, O., Akter, K.-M., Kim, D., Yang, J., & Kim, D. R. (2022) · Antioxidants · doi:10.3390/antiox11081571 · Cited by 34
“VPS34 complex proteins help form the phagophore that is then processed into an autophagosome through lipidation of LC3 with phosphatidylethanolamine (PE) by another complex that includes ATG16, ATG5, and ATG12 [251].”
BackgroundStudying plant autophagy: challenges and recommended methodologies
Qi, H., Wang, Y., Bao, Y., Bassham, D. C., Chen, L., Chen, Q., Hou, S., Hwang, I., Huang, L., Lai, Z., et al. (2023) · Advanced Biotechnology · doi:10.1007/s44307-023-00002-8 · Cited by 36
“…processed by the ATG4 protease to expose a C-terminal glycine residue and is covalently modified with the attachment of the membrane lipid PE via ubiquitin-like reactions that promote the formation of the ATG8–PE adduct (Ohsumi 2001; Yoshimoto et al. 2004; Hanada et al. 2007; Fujita et al. 2008).”
BackgroundJiang, L., Yuan, F., Yin, X., & Dong, J. (2014) · Connective Tissue Research · doi:10.3109/03008207.2014.942419 · Cited by 33
The Role of Autophagy in the Resistance to BRAF Inhibition in BRAF-Mutated Melanoma
Liu, X., Wu, J., Qin, H., & Xu, J. (2018) · Targeted Oncology · doi:10.1007/s11523-018-0565-2 · Cited by 36
Ye, Y., Tyndall, E. R., Bui, V., Tang, Z., Shen, Y., Jiang, X., Flanagan, J. M., Wang, H., & Tian, F. (2021) · Nature Communications · doi:10.1038/s41467-020-20607-0 · Cited by 35
Maggi, F., Morelli, M. B., Tomassoni, D., Marinelli, O., Aguzzi, C., Zeppa, L., Nabissi, M., Santoni, G., & Amantini, C. (2021) · Cancer Science · doi:10.1111/cas.15257 · Cited by 34
Autophagy as a Stress Response Pathway in the Immune System
Bhattacharya, A., & Eissa, N. T. (2015) · International Reviews of Immunology · doi:10.3109/08830185.2014.999156 · Cited by 37
“This complex remains on the outer side of the phagophore, is essential for phagophore elongation [2] and can act as a novel E3-like enzyme determining the site of action of the ATG8 (LC3) conjugation system [24, 25], the second UBL conjugation system.”
BackgroundAutophagy/Mitophagy Regulated by Ubiquitination: A Promising Pathway in Cancer Therapeutics
Jee, S.-C., & Cheong, H. (2023) · Cancers · doi:10.3390/cancers15041112 · Cited by 34
“ATG12 Involved in phagophore elongation, a ubiquitin-like modifier that forms the ATG12–ATG5 complex, which acts as an E3 complex in ATG8–PE conjugation [54,55]”
BackgroundWang, B.-R., Han, J.-B., Jiang, Y., et al. (2023) · Autophagy · doi:10.1080/15548627.2023.2258052 · Cited by 33
“ATG5 (autophagy related 5) plays an important role in regulating the initiation and formation of autophagosomes [14].”
BackgroundTumor endothelial cell autophagy is a key vascular‐immune checkpoint in melanoma
Verhoeven, J., Jacobs, K., Rizzollo, F., Lodi, F., Hua, Y., Poźniak, J., Srinivasan, A. N., Houbaert, D., Shankar, G., More, S., et al. (2023) · EMBO Molecular Medicine · doi:10.15252/emmm.202318028 · Cited by 35
Aggrephagy: lessons from C. elegans
Lu, Q., Wu, F., & Zhang, H. (2013) · Biochemical Journal · doi:10.1042/bj20121721 · Cited by 35
Chen, Q., Yue, F., Li, W., Zou, J., Xu, T., Huang, C., Zhang, Y., Song, K., Huang, G., Xu, G., et al. (2015) · Journal of Biological Chemistry · doi:10.1074/jbc.m115.653568 · Cited by 27
“The LC3 precursor is truncated to form the cytosolic LC3-I and further conjugated with phosphatidylethanolamine to create the membraneassociated LC3-II with the assistance of ATG5 and ATG12 (5, 6).”
BackgroundStructure and Dynamics in the ATG8 Family From Experimental to Computational Techniques
Sora, V., Kumar, M., Maiani, E., Lambrughi, M., Tiberti, M., & Papaleo, E. (2020) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2020.00420 · Cited by 33
“BNIP3 interacts with higher affinity with LC3B (Hanna et al., 2012; Zhu et al., 2013), weakly with GABARAPL2 (Zhu et al., 2013) and not with GABARAP (Hanna et al., 2012) or GABARAPL1 (Zhu et al., 2013).”
BackgroundXu, C., Zang, Y., Zhao, Y., Cui, W., Zhang, H., Zhu, Y., & Xu, M. (2021) · Frontiers in Oncology · doi:10.3389/fonc.2021.652211 · Cited by 34
“Autophagy related protein 5 (ATG5) is an important autophagosome formation related protein that functions as an E1-like activating enzyme in eukaryotic cells (1, 2).”
BackgroundLiang, Q., Wan, J., Liu, H., et al. (2022) · Autophagy · doi:10.1080/15548627.2022.2091904 · Cited by 33
“A key event in the biogenesis of autophagosomes is the recruitment of ATG12–ATG5 conjugate to facilitate the covalent attachment of ATG8 to PE lipids on the nascent phagophore membrane [42].”
BackgroundThe Atg1 complex, Atg9, and Vac8 recruit PI3K complex I to the pre-autophagosomal structure
Hitomi, K., Kotani, T., Noda, N. N., Kimura, Y., & Nakatogawa, H. (2023) · The Journal of Cell Biology · doi:10.1083/jcb.202210017 · Cited by 33
“Finally, Atg8 is conjugated to phosphatidylethanolamine (PE) in pre-autophagosomal membranes at the PAS via ubiquitin-like conjugation reactions, during which the Atg16 complex serves as an E3 enzyme (Ichimura et al., 2000; Hanada et al., 2007; Suzuki et al., 2007).”
Self-citationPhadwal, K., Kurian, D., Salamat, M. K. F., MacRae, V. E., Diack, A. B., & Manson, J. C. (2018) · Scientific Reports · doi:10.1038/s41598-018-28296-y · Cited by 33
Jia, H., Wei, J., Zheng, W., & Li, Z. Y. (2025) · Journal of Translational Medicine · doi:10.1186/s12967-025-06595-z · Cited by 33
“This mechanism allows for the generation of the lipidated version of LC3 via the incorporation of the ATG5-ATG12 E3 ubiquitin ligase [119].”
Size, stoichiometry, and organization of soluble LC3-associated complexes
Kraft, L. J., Nguyen, T. A., Vogel, S. S., & Kenworthy, A. K. (2014) · Autophagy · doi:10.4161/auto.28175 · Cited by 31
It takes two to tango: Ubiquitin and SUMO in the DNA damage response
Bologna, S., & Ferrari, S. M. (2013) · Frontiers in Genetics · doi:10.3389/fgene.2013.00106 · Cited by 33
“This consists of the E1like enzyme Atg7, the E2-like components Atg3 and Atg7, and the E3-like Atg12-Atg5 conjugate that facilitates transfer of the Ubiquitin-like modifier Atg8 to phospholipids (Hanada et al., 2007).”
BackgroundEvolutionary diversification of the autophagy-related ubiquitin-like conjugation systems
Zhang, S., Yazaki, E., Sakamoto, H., Yamamoto, H., & Mizushima, N. (2022) · Autophagy · doi:10.1080/15548627.2022.2059168 · Cited by 34
“In fact, the present-day species such as yeast, Toxoplasma, and Arabidopsis can form lipidated ATG8 without the ATG12–ATG5-ATG16 complex in vitro, albeit at a lower efficiency [34,64,89].”
BackgroundAutophagosomal Protein Dynamics and Influenza Virus Infection
Dumit, V. I., & Dengjel, J. (2012) · Frontiers in Immunology · doi:10.3389/fimmu.2012.00043 · Cited by 31
Wang, Z., Hu, J. N., Li, G., Qu, L., He, Q., Lou, Y., Song, Q., Ma, D., & Chen, Y. (2014) · Autophagy · doi:10.4161/auto.36439 · Cited by 31
Dysregulation of M segment gene expression contributes to influenza A virus host restriction
Calderon, B. M., Danzy, S., Delima, G. K., Jacobs, N. T., Ganti, K., Hockman, M. R., Conn, G. L., Lowen, A. C., & Steel, J. (2019) · PLoS Pathogens · doi:10.1371/journal.ppat.1007892 · Cited by 32
“through the addition of phosphotidylethanolamine [57,58].”
Li, Y., Sha, Y., Wang, H., He, L., Li, L., Wen, S., Sheng, L., Hu, W., & Zhou, H. (2021) · The FASEB Journal · doi:10.1096/fj.202100856r · Cited by 31
Canonical and non-canonical roles for ATG8 proteins in autophagy and beyond
Reid, S. E., Kolapalli, S. P., Nielsen, T. M., & Frankel, L. B. (2022) · Frontiers in Molecular Biosciences · doi:10.3389/fmolb.2022.1074701 · Cited by 31
“specific glycine residue of ATG8 is performed by collaborative activities of the E2-like ATG3 and E3-like ATG12-ATG5ATG16L1 complexes (Hanada et al., 2007; Geng and Klionsky, 2008; Sakoh-Nakatogawa et al., 2013).”
BackgroundCooperation between proteolytic systems in cardiomyocyte recycling
Yamaguchi, O., Taneike, M., & Otsu, K. (2012) · Cardiovascular Research · doi:10.1093/cvr/cvs236 · Cited by 31
HMGA2 plays an important role in Cr (VI)‐induced autophagy
Yang, F., Zhao, L., Mei, D., Jiang, L., Geng, C., Li, Q., Yao, X., Liu, Y., Kong, Y., & Cao, J. (2017) · International Journal of Cancer · doi:10.1002/ijc.30789 · Cited by 31
“Atg12-Atg5 complex contributes to elongation and closure of the autophagosomes and it is essential for LC3 lipidation and targeting.(34,35) Which acts upstream of autophagosomes formation, governs the autophagy process by the subsequent recruitment of additional autophagy-related proteins for initiating autophagosomes…”
BackgroundSingapore Grouper Iridovirus (SGIV) Inhibited Autophagy for Efficient Viral Replication
Li, C., Wang, L., Liu, J., Yu, Y., Huang, Y., Huang, X., Wei, J., & Qin, Q. (2020) · Frontiers in Microbiology · doi:10.3389/fmicb.2020.01446 · Cited by 30
“The Atg5-Atg12 conjugate has E3-like activity for LC3 lipidation (Hanada et al., 2007; Mizushima et al., 2011).”
BackgroundRegulation of autophagy by protein methylation and acetylation in cancer
Jeon, M., Park, J., Yang, E., Baek, H., & Kim, H.-K. (2021) · Journal of Cellular Physiology · doi:10.1002/jcp.30502 · Cited by 32
“PE conjugates into the membrane of the phagophore (Hanada et al., 2007; Suzuki & Ohsumi, 2010; Xie et al., 2008).”
BackgroundCell Autophagy in NASH and NASH-Related Hepatocellular Carcinoma
Udoh, U. S., Rajan, P. K., Nakafuku, Y., Finley, R., & Sanabria, J. R. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms23147734 · Cited by 30
Cui, J., Ogasawara, Y., Kurata, I., Matoba, K., Fujioka, Y., Noda, N. N., Shibasaki, M., & Watanabe, T. (2022) · Journal of the American Chemical Society · doi:10.1021/jacs.2c07648 · Cited by 32
Self-citationSolution structure of Atg8 reveals conformational polymorphism of the N-terminal domain
Schwarten, M., Stoldt, M., Mohrlüder, J., & Willbold, D. (2010) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2010.04.043 · Cited by 30
Ma, L., Chu, W., Chai, J., Shen, C., Li, D., & Wang, X. (2017) · PLoS ONE · doi:10.1371/journal.pone.0186128 · Cited by 30
Transglutaminase type 2 in the regulation of proteostasis
D’Eletto, M., Rossin, F., Fedorova, O., Farrace, M. G., & Piacentini, M. (2018) · Biological Chemistry · doi:10.1515/hsz-2018-0217 · Cited by 32
Wang, X., Gao, Y., Yan, Q., & Chen, W. (2016) · Acta Physiologiae Plantarum · doi:10.1007/s11738-016-2257-9 · Cited by 29
“Keywords Arabidopsis Autophagy Cell death NPR3 NPR4 Senescence”
BackgroundStructure of the WD40‐domain of human ATG16L1
Bajagic, M., Archna, A., Büsing, P., & Scrima, A. (2017) · Protein Science · doi:10.1002/pro.3222 · Cited by 31
“The E3-ligase complex conjugates phosphatidylethanolamine (PE) to LC3 (the mammalian homolog of yeast ATG8) and determines the site of conjugation during autophagosome biogenesis.(21,22) Further studies on the function of the yeast E3-ligase complex showed that ATG12 ATG5/ATG16, in addition to directly binding to memb…”
BackgroundATG8ylation of proteins: A way to cope with cell stress?
Carosi, J. M., Nguyen, T. N., Lazarou, M., Kumar, S., & Sargeant, T. J. (2021) · The Journal of Cell Biology · doi:10.1083/jcb.202108120 · Cited by 30
Visualization of Atg3 during Autophagosome Formation in Saccharomyces cerevisiae
Ngu, M., Hirata, E., & Suzuki, K. (2015) · Journal of Biological Chemistry · doi:10.1074/jbc.m114.626952 · Cited by 30
“Activated Atg8 is transferred from Atg7 to the E2-like enzyme Atg3 (15) and ultimately attached to the amino group of PE by interacting with the E3-like Atg16 Atg5-Atg12 complex (16, 17).”
BackgroundChung, Y., Choi, B., Song, D., Song, Y., Kang, S., Yoon, S., Kim, S. W., Lee, H. K., & Chang, E. (2014) · The International Journal of Biochemistry & Cell Biology · doi:10.1016/j.biocel.2014.07.018 · Cited by 29
Li, Y., Zhang, L., Li, K., et al. (2015) · Scientific Reports · doi:10.1038/srep09288 · Cited by 29
Atg3-Mediated Lipidation of Atg8 Is Involved in Encystation ofAcanthamoeba
Moon, E., Chung, D.-I., Hong, Y., et al. (2011) · Korean Journal of Parasitology · doi:10.3347/kjp.2011.49.2.103 · Cited by 29
“Atg3 functions as an E2-like enzyme during the initial stages of autophagosome formation by catalyzing the transfer of Atg7 bound Atg8 (known as LC3, GATE16, and GABA-RAP in mammals) to PE, the critical step for autophagy [20].”
BackgroundPI3K-C2α knockdown decreases autophagy and maturation of endocytic vesicles
Merrill, N. M., Schipper, J. L., Karnes, J., Kauffman, A. L., Martin, K. R., & MacKeigan, J. P. (2017) · PLoS ONE · doi:10.1371/journal.pone.0184909 · Cited by 34
Ramachandra Rao, S., Pfeffer, B. A., Más Gómez, N., Skelton, L. A., Keiko, U., Sparrow, J. R., Rowsam, A. M., Mitchell, C. H., & Fliesler, S. J. (2018) · Autophagy · doi:10.1080/15548627.2018.1490851 · Cited by 28
Roles of mitophagy in cellular physiology and development
Dengjel, J., & Abeliovich, H. (2016) · Cell and Tissue Research · doi:10.1007/s00441-016-2472-0 · Cited by 28
Methylomic correlates of autophagy activity in cystic fibrosis
Caution, K., Pan, A., Krause, K., Badr, A., Hamilton, K., Vaidya, A., Gosu, H., Daily, K. P., Estfanous, S. Z. K., Gavrilin, M. A., et al. (2019) · Journal of Cystic Fibrosis · doi:10.1016/j.jcf.2019.01.011 · Cited by 28
Xie, X., Hu, L., Liu, L., Wang, J., Liu, Y., Ma, L., Sun, G., Li, C., Aisa, H. A., & Meng, S. (2022) · Translational Oncology · doi:10.1016/j.tranon.2022.101388 · Cited by 28
“Meanwhile, the LC3-II levels in the punicalagin (140 or 90 μM)/chloroquine-co-treated cells were upregulated when compared with those in the punicalagin (140 or 90 μM)-treated and chloroquine-treated cells (Fig.”
BackgroundInfluentialWang, Y., Yao, Y., Wang, C., Wang, B., Zou, W., Zhang, N., & Chen, X. (2022) · Frontiers in Nutrition · doi:10.3389/fnut.2022.858261 · Cited by 28
“ATG5 is a key ATG protein that is involved in autophagy by forming a complex with ATG12 that promotes the transformation of LC3-II and autophagy precursors (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
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
