Two Beclin 1-binding proteins, Atg14L and Rubicon, reciprocally regulate autophagy at different stages

Matsunaga, Kohichi; Saitoh, Tatsuya; Tabata, Keisuke; Omori, Hiroko; Satoh, Takashi; Kurotori, Naoki; Maejima, Ikuko; Shirahama-Noda, Kanae; Ichimura, Tohru; Isobe, Toshiaki; Akira, Shizuo; Noda, Takeshi; Yoshimori, Tamotsu

doi:10.1038/ncb1846

Cited by 1,235Autophagy in Disease and TherapyCellular transport and secretionCalcium signaling and nucleotide metabolism

Two Beclin 1-binding proteins, Atg14L and Rubicon, reciprocally regulate autophagy at different stages

Matsunaga, Kohichi, Saitoh, Tatsuya, Tabata, Keisuke, Omori, Hiroko, Satoh, Takashi, Kurotori, Naoki, Maejima, Ikuko, Shirahama-Noda, Kanae +5 more·2009·Nature Cell Biology

DOI 10.1038/ncb1846

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Abstract

Beclin 1, a protein essential for autophagy, binds to hVps34/Class III phosphatidylinositol-3-kinase and UVRAG. Here, we have identified two Beclin 1 associated proteins, Atg14L and Rubicon. Atg14L and UVRAG bind to Beclin 1 in a mutually exclusive manner, whereas Rubicon binds only to a subpopulation of UVRAG complexes; thus, three different Beclin 1 complexes exist. GFP-Atg14L localized to the isolation membrane and autophagosome, as well as to the ER and unknown puncta. Knockout of Atg14L in mouse ES cells caused a defect in autophagosome formation. GFP-Rubicon was localized at the endosome/lysosome. Knockdown of Rubicon caused enhancement of autophagy, especially at the maturation step, as well as enhancement of endocytic trafficking. These data suggest that the Beclin 1-hVps34 complex functions in two different steps of autophagy by altering the subunit composition.

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Yeast Atg14 is the autophagy-specific subunit of the Vps34 complex I, and a human homolog named ATG14 (ATG14L/BARKOR) has been identified.
“Yeast Atg14 is the autophagy-specific subunit of the Vps34 complex I, 404 and a human homolog, named ATG14 (ATG14L/BARKOR), has been identified.[405][406][407][408]”
From Guidelines for the use and interpretation of assays for monitoring autophagy (2012) · cites this paper as [405]
RUBCN is an inhibitor of autophagy, localizing to late endosomes/lysosomes to inhibit autophagosome maturation.
“Interestingly, while RUBCN is a LAP-specific mediator, it is also an inhibitor of autophagy, localizing to late endosomes/lysosomes to inhibit autophagosome maturation.21,22”
From RUBCN/rubicon and EGFR regulate lysosomal degradative processes in the retinal pigment epithelium (RPE) of the eye (2017) · cites this paper as [22]
Rubicon is an inhibitor of canonical autophagy and a key component of a non-canonical function of autophagy proteins that modulates inflammatory immune activation.
“Rubicon has been shown to be an inhibitor of canonical autophagy (Matsunaga et al., 2009) and a key component of a non-canonical function of autophagy proteins that modulates inflammatory immune activation (Cunha et al., 2018; Martinez et al., 2016).”
From LC3-Associated Endocytosis Facilitates β-Amyloid Clearance and Mitigates Neurodegeneration in Murine Alzheimer’s Disease (2019) · cites this paper as Matsunaga et al., 2009

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Kabeya, Y., Mizushima, N., Ueno, T., Yamamoto, A., Kirisako, T., Noda, T., Kominami, E., Ohsumi, Y., & Yoshimori, T. (2000) · The EMBO Journal · doi:10.1093/emboj/19.21.5720 · Cited by 6,605 · see citing works
Self-citation
Autophagy: process and functionPreprint
Mizushima, N. (2007) · Genes & Development · doi:10.1101/gad.1599207 · Cited by 3,964 · see citing works
Suppression of basal autophagy in neural cells causes neurodegenerative disease in mice
Hara, T., Nakamura, K., Matsui, M., Yamamoto, A., Nakahara, Y., Suzuki-Migishima, R., Yokoyama, M., Mishima, K., Saito, I., Okano, H., et al. (2006) · Nature · doi:10.1038/nature04724 · Cited by 3,882 · see citing works
Development by Self-Digestion
Levine, B., & Klionsky, D. J. (2004) · Developmental Cell · doi:10.1016/s1534-5807(04)00099-1 · Cited by 3,671 · see citing works
Bcl-2 Antiapoptotic Proteins Inhibit Beclin 1-Dependent Autophagy
Pattingre, S., Tassa, A., Qu, X., Garuti, R., Liang, X. H., Mizushima, N., Packer, M., Schneider, M. D., & Levine, B. (2005) · Cell · doi:10.1016/j.cell.2005.07.002 · Cited by 3,536 · see citing works
Loss of autophagy in the central nervous system causes neurodegeneration in mice
Komatsu, M., Waguri, S., Chiba, T., Murata, S., Iwata, J.-I., Tanida, I., Ueno, T., Koike, M., Uchiyama, Y., Kominami, E., et al. (2006) · Nature · doi:10.1038/nature04723 · Cited by 3,500 · see citing works
Induction of autophagy and inhibition of tumorigenesis by beclin 1
Liang, X. H., Jackson, S., Seaman, M., Brown, K., Kempkes, B., Hibshoosh, H., & Levine, B. (1999) · Nature · doi:10.1038/45257 · Cited by 3,347 · see citing works
p62/SQSTM1 forms protein aggregates degraded by autophagy and has a protective effect on huntingtin-induced cell death
Bjørkøy, G., Lamark, T., Brech, A., Outzen, H., Perander, M., Øvervatn, A., Stenmark, H., & Johansen, T. (2005) · The Journal of Cell Biology · doi:10.1083/jcb.200507002 · Cited by 3,276 · see citing works
Genomic Libraries and a Host Strain Designed for Highly Efficient Two-Hybrid Selection in Yeast
James, P. M., Halladay, J. T., & Craig, E. A. (1996) · Genetics · doi:10.1093/genetics/144.4.1425 · Cited by 2,638 · see citing works
Promotion of tumorigenesis by heterozygous disruption of the beclin 1 autophagy gene
Qu, X., Yu, J., Bhagat, G., Furuya, N., Hibshoosh, H., Troxel, A., Rosen, J., Eskelinen, E.-L., Mizushima, N., Ohsumi, Y., et al. (2003) · Journal of Clinical Investigation · doi:10.1172/jci20039 · Cited by 2,311 · see citing works
Homeostatic levels of p62 control cytoplasmic inclusion body formation in autophagy-deficient mice.
Komatsu, M., Waguri, S., Koike, M., Sou, Y.-S., Ueno, T., Hara, T., Mizushima, N., Iwata, J.-I., Ezaki, J., Murata, S., et al. (2007) · Cell · doi:10.1016/j.cell.2007.10.035 · Cited by 2,124 · see citing works
Beclin 1, an autophagy gene essential for early embryonic development, is a haploinsufficient tumor suppressor
Yue, Z., Jin, S., Yang, C., Levine, A. J., & Heintz, N. (2003) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2436255100 · Cited by 2,116 · see citing works
Autophagosome formation from membrane compartments enriched in phosphatidylinositol 3-phosphate and dynamically connected to the endoplasmic reticulum
Axe, E. L., Walker, S. A., Manifava, M., Chandra, P., Roderick, H. L., Habermann, A., Griffiths, G., & Ktistakis, N. T. (2008) · The Journal of Cell Biology · doi:10.1083/jcb.200803137 · Cited by 1,885 · see citing works
Plat-E: an efficient and stable system for transient packaging of retroviruses
MORITA, S., Kojima, T., & Kitamura, T. (2000) · Gene Therapy · doi:10.1038/sj.gt.3301206 · Cited by 1,660 · see citing works
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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 · see citing works
Self-citation
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Shimizu, S., Kanaseki, T., Mizushima, N., Mizuta, T., Arakawa-Kobayashi, S., Thompson, C. B., & Tsujimoto, Y. (2004) · Nature Cell Biology · doi:10.1038/ncb1192 · Cited by 1,358 · see citing works
Cloning, structure, and expression of the mitochondrial cytochrome P-450 sterol 26-hydroxylase, a bile acid biosynthetic enzyme
Andersson, S., Davis, D. L., Dahlbäck, H., Jörnvall, H., & Russell, D. W. (1989) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)83172-6 · Cited by 1,229 · see citing works
Regulation of an ATG7 - beclin 1 Program of Autophagic Cell Death by Caspase-8
Yu, L., Alva, A. S., Su, H. C., Dutt, P., Freundt, E. C., Welsh, S. J., Baehrecke, E. H., & Lenardo, M. J. (2004) · Science · doi:10.1126/science.1096645 · Cited by 1,220 · see citing works
Beclin 1 Forms Two Distinct Phosphatidylinositol 3-Kinase Complexes with Mammalian Atg14 and UVRAG
Itakura, E., Kishi, C., Inoue, K., & Mizushima, N. (2008) · Molecular Biology of the Cell · doi:10.1091/mbc.e08-01-0080 · Cited by 1,176 · see citing works
Distinct Classes of Phosphatidylinositol 3′-Kinases Are Involved in Signaling Pathways That Control Macroautophagy in HT-29 Cells
Petiot, A., Ogier‐Denis, É., Blommaart, E. F. C., Meijer, A. J., & Codogno, P. (2000) · Journal of Biological Chemistry · doi:10.1074/jbc.275.2.992 · Cited by 1,168 · see citing works
Lysosomal turnover, but not a cellular level, of endogenous LC3 is a marker for autophagy
Tanida, I., Minematsu-Ikeguchi, N., Ueno, T., & Kominami, E. (2005) · Autophagy · doi:10.4161/auto.1.2.1697 · Cited by 1,108 · cited 1× · see citing works
“LC3-II on the autophagosome inner membrane is finally degraded on fusion of autophagosomes and lysosome”
Background
Functional and physical interaction between Bcl‐XL and a BH3‐like domain in Beclin‐1
Maiuri, M. C., Toumelin-Braizat, G. L., Criollo, A., Rain, J., Gautier, F., Juin, P. P., Tasdemir, E., Pierron, G., Troulinaki, K., Tavernarakis, N., et al. (2007) · The EMBO Journal · doi:10.1038/sj.emboj.7601689 · Cited by 1,107 · see citing works
Autophagy Defends Cells Against Invading Group A Streptococcus
Nakagawa, I., Amano, A., Mizushima, N., Yamamoto, A., Yamaguchi, H., Kamimoto, T., Nara, A., Funao, J., Nakata, M., Tsuda, K., et al. (2004) · Science · doi:10.1126/science.1103966 · Cited by 1,091 · see citing works
Self-citation
The Atg16L Complex Specifies the Site of LC3 Lipidation for Membrane Biogenesis in Autophagy
Fujita, N., Itoh, T., Omori, H., Fukuda, M., Noda, T., & Yoshimori, T. (2008) · Molecular Biology of the Cell · doi:10.1091/mbc.e07-12-1257 · Cited by 1,083 · see citing works
Self-citation
Ambra1 regulates autophagy and development of the nervous system
Fimia, G. M., Stoykova, A., Romagnoli, A., Giunta, L., Bartolomeo, S. D., Nardacci, R., Corazzari, M., Fuoco, C., Uçar, A., Schwartz, P. J., et al. (2007) · Nature · doi:10.1038/nature05925 · Cited by 1,048 · see citing works
Autophagic and tumour suppressor activity of a novel Beclin1-binding protein UVRAG
Liang, C., Feng, P., Ku, B., Dotan, I., Canaani, D., Oh, B., & Jung, J. U. (2006) · Nature Cell Biology · doi:10.1038/ncb1426 · Cited by 1,025 · see citing works
Two Distinct Vps34 Phosphatidylinositol 3–Kinase Complexes Function in Autophagy and Carboxypeptidase Y Sorting in Saccharomyces cerevisiae
Kihara, A., Noda, T., Ishihara, N., & Ohsumi, Y. (2001) · The Journal of Cell Biology · doi:10.1083/jcb.152.3.519 · Cited by 1,004 · see citing works
Self-citation
Role and Regulation of Starvation-Induced Autophagy in the Drosophila Fat Body
Scott, R. C., Schuldiner, O., & Neufeld, T. P. (2004) · Developmental Cell · doi:10.1016/j.devcel.2004.07.009 · Cited by 963 · see citing works
Bif-1 interacts with Beclin 1 through UVRAG and regulates autophagy and tumorigenesis
Takahashi, Y., Coppola, D., Matsushita, N., Cualing, H. D., Sun, M., Sato, Y., Liang, C., Jung, J. U., Cheng, J. Q., Mul, J. J., et al. (2007) · Nature Cell Biology · doi:10.1038/ncb1634 · Cited by 928 · see citing works
The Phosphatidylinositol 3‐Kinase Inhibitors Wortmannin and LY294002 Inhibit Autophagy in Isolated Rat Hepatocytes
Blommaart, E. F. C., Krause, U., Schellens, J. P. M., Vreeling‐Sindelárová, H., & Meijer, A. J. (1997) · European Journal of Biochemistry · doi:10.1111/j.1432-1033.1997.0240a.x · Cited by 870 · see citing works
Endogenous MHC Class II Processing of a Viral Nuclear Antigen After Autophagy
Paludan, C., Schmid, D., Landthaler, M., Vockerodt, M., Kube, D., Tuschl, T., & Münz, C. (2005) · Science · doi:10.1126/science.1104904 · Cited by 860 · see citing works
Beclin–phosphatidylinositol 3‐kinase complex functions at the trans‐Golgi network
Kihara, A., Kabeya, Y., Ohsumi, Y., & Yoshimori, T. (2001) · The EMBO Reports · doi:10.1093/embo-reports/kve061 · Cited by 813 · see citing works
Self-citation
Beclin1-binding UVRAG targets the class C Vps complex to coordinate autophagosome maturation and endocytic trafficking
Liang, C., Lee, J.-S., Inn, K.-S., Gack, M. U., Li, Q., Roberts, E. A., Vergne, I., Deretic, V., Feng, P., Akazawa, C., et al. (2008) · Nature Cell Biology · doi:10.1038/ncb1740 · Cited by 792 · see citing works
Mouse Apg16L, a novel WD-repeat protein, targets to the autophagic isolation membrane with the Apg12-Apg5 conjugate
Mizushima, N., Kuma, A., Kobayashi, Y., Yamamoto, A., Matsubae, M., Takao, T., Natsume, T., Ohsumi, Y., & Yoshimori, T. (2003) · Journal of Cell Science · doi:10.1242/jcs.00381 · Cited by 791 · see citing works
Self-citation
Chaperone-Mediated Autophagy
Dice, J. F. (2007) · Autophagy · doi:10.4161/auto.4144 · Cited by 569 · see citing works
Identification of Barkor as a mammalian autophagy-specific factor for Beclin 1 and class III phosphatidylinositol 3-kinase
Sun, Q., Fan, W., Chen, K., Ding, X., Chen, S., & Zhong, Q. (2008) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0810452105 · Cited by 504 · see citing works
Dynein-dependent Movement of Autophagosomes Mediates Efficient Encounters with Lysosomes
Kimura, S., Noda, T., & Yoshimori, T. (2008) · Cell Structure and Function · doi:10.1247/csf.08005 · Cited by 434 · see citing works
Self-citation
The Evolutionarily Conserved Domain of Beclin 1 is Required for Vps34 Binding, Autophagy, and Tumor Suppressor Function
Furuya, N., Yu, J., Byfield, M. P., Pattingre, S., & Levine, B. (2005) · Autophagy · doi:10.4161/auto.1.1.1542 · Cited by 430 · see citing works
Regulation of membrane traffic by phosphoinositide 3-kinases
Lindmo, K., & Stenmark, H. (2006) · Journal of Cell Science · doi:10.1242/jcs.02855 · Cited by 425 · see citing works
Endosome to Golgi Retrieval of the Vacuolar Protein Sorting Receptor, Vps10p, Requires the Function of the VPS29, VPS30, and VPS35 Gene Products
Seaman, M. N. J., Marcusson, E. G., Cereghino, J. L., & Emr, S. D. (1997) · The Journal of Cell Biology · doi:10.1083/jcb.137.1.79 · Cited by 412 · see citing works
Amino Acids Activate mTOR Complex 1 via Ca2+/CaM Signaling to hVps34
Gulati, P., Gaspers, L. D., Dann, S. G., Joaquin, M., Nobukuni, T., Natt, F., Kozma, S. C., Thomas, A. P., & Thomas, G. (2008) · Cell Metabolism · doi:10.1016/j.cmet.2008.03.002 · Cited by 371 · see citing works
Functional specificity of the mammalian Beclin-Vps34 PI 3-kinase complex in macroautophagy versus endocytosis and lysosomal enzyme trafficking
Zeng, X., Overmeyer, J. H., & Maltese, W. A. (2006) · Journal of Cell Science · doi:10.1242/jcs.02735 · Cited by 331 · see citing works
Apg14p and Apg6/Vps30p Form a Protein Complex Essential for Autophagy in the Yeast, Saccharomyces cerevisiae
Kametaka, S., Okano, T., Ohsumi, M., & Ohsumi, Y. (1998) · Journal of Biological Chemistry · doi:10.1074/jbc.273.35.22284 · Cited by 275 · see citing works
Assortment of Phosphatidylinositol 3-Kinase Complexes—Atg14p Directs Association of Complex I to the Pre-autophagosomal Structure inSaccharomyces cerevisiae
Obara, K., Sekito, T., & Ohsumi, Y. (2006) · Molecular Biology of the Cell · doi:10.1091/mbc.e05-09-0841 · Cited by 229 · see citing works
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Ropolo, A., Grasso, D., Pardo, R., Sacchetti, M. L., Archange, C., Re, A. L., Seux, M., Nowak, J., Gonzalez, C. D., Iovanna, J. L., et al. (2007) · Journal of Biological Chemistry · doi:10.1074/jbc.m706956200 · Cited by 223 · see citing works
Retromer function in endosome-to-Golgi retrograde transport is regulated by the yeast Vps34 PtdIns 3-kinase
Burda, P., Padilla, S. M., Sarkar, S., & Emr, S. D. (2002) · Journal of Cell Science · doi:10.1242/jcs.00090 · Cited by 216 · see citing works
Class III phosphoinositide 3-kinase–Beclin1 complex mediates the amino acid-dependent regulation of autophagy in C2C12 myotubes
Tassa, A., Roux, M.-P., Attaix, D., & Béchet, D. (2003) · Biochemical Journal · doi:10.1042/bj20030826 · Cited by 207 · see citing works
Vam7p, a SNAP-25-Like Molecule, and Vam3p, a Syntaxin Homolog, Function Together in Yeast Vacuolar Protein Trafficking
Sato, T. K., Darsow, T., & Emr, S. D. (1998) · Molecular and Cellular Biology · doi:10.1128/mcb.18.9.5308 · Cited by 197 · see citing works
14-3-3 Proteins Modulate the Expression of Epithelial Na+ Channels by Phosphorylation-dependent Interaction with Nedd4-2 Ubiquitin Ligase
Ichimura, T., Yamamura, H., Sasamoto, K., Tominaga, Y., Taoka, M., Kakiuchi, K., Shinkawa, T., Takahashi, N., Shimada, S., & Isobe, T. (2005) · Journal of Biological Chemistry · doi:10.1074/jbc.m412884200 · Cited by 193 · see citing works
Self-citation
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Müller, O., Sattler, T., Floetenmeyer, M., Schwarz, H., Plattner, H., & Mayer, A. (2000) · The Journal of Cell Biology · doi:10.1083/jcb.151.3.519 · Cited by 173 · see citing works
HUGE: a database for human large proteins identified in the Kazusa cDNA sequencing project
Kikuno, R. F. (2000) · Nucleic Acids Research · doi:10.1093/nar/28.1.331 · Cited by 149 · see citing works
RUN domains: a new family of domains involved in Ras-like GTPase signaling
Callebaut, I., Jean, de Gunzburg, Goud, B., & Mornon, J.-P. (2001) · Trends in Biochemical Sciences · doi:10.1016/s0968-0004(00)01730-8 · Cited by 96 · see citing works
HUGE: a database for human large proteins identified in the Kazusa cDNA sequencing project
Kikuno, R. F. (2002) · Nucleic Acids Research · doi:10.1093/nar/30.1.166 · Cited by 82 · see citing works
Phosphoinositide‐Regulated Retrograde Transport of Ricin: Crosstalk Between hVps34 and Sorting Nexins
Skånland, S. S., Wälchli, S., Utskarpen, A., Wandinger‐Ness, A., & Sandvig, K. (2006) · Traffic · doi:10.1111/j.1600-0854.2006.00527.x · Cited by 57 · see citing works
WatershedCounting3D: A New Method for Segmenting and Counting Punctate Structures from Confocal Image Data
Gniadek, T. J., & Warren, G. (2007) · Traffic · doi:10.1111/j.1600-0854.2007.00538.x · Cited by 32 · see citing works
Post-Translational Targeting of a Tail-Anchored Green Fluorescent Protein to the Endolpasmic Reticulum
Masaki, R. (2003) · The Journal of Biochemistry · doi:10.1093/jb/mvg159 · Cited by 12 · see citing works

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Klionsky, D. J., Abdelmohsen, K., Abe, A., Abedin, M. J., Abeliovich, H., Acevedo Arozena, A., Adachi, H., Adams, C. M., Adams, P. D., Adeli, K., et al. (2016) · Autophagy · doi:10.1080/15548627.2015.1100356 · Cited by 5,894 · see citing works
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Self-citation
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Self-citation
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“Rubicon has been shown to be an inhibitor of canonical autophagy (Matsunaga et al., 2009) and a key component of a noncanonical function of autophagy proteins that modulates inflammatory immune activation (Cunha et al.”
Defective CFTR induces aggresome formation and lung inflammation in cystic fibrosis through ROS-mediated autophagy inhibition
Luciani, A., Villella, V. R., Esposito, S., Brunetti-Pierri, N., Medina, D., Settembre, C., Gavina, M., Pulze, L., Giardino, I., Pettoello-Mantovani, M., et al. (2010) · Nature Cell Biology · doi:10.1038/ncb2090 · Cited by 467 · see citing works
Biogenesis and Cargo Selectivity of Autophagosomes
Weidberg, H., Shvets, E., & Elazar, Z. (2011) · Annual Review of Biochemistry · doi:10.1146/annurev-biochem-052709-094552 · Cited by 466 · see citing works
MAPK/JNK signalling: a potential autophagy regulation pathway
Zhou, Y.-Y., Li, Y., Jiang, W.-Q., & Zhou, L.-F. (2015) · Bioscience Reports · doi:10.1042/bsr20140141 · Cited by 444 · see citing works
Autophagy in osteoblasts is involved in mineralization and bone homeostasis
Nollet, M., Santucci-Darmanin, S., Breuil, V., Al-Sahlanee, R., Cros, C., Topi, M., Momier, D., Samson, M., Pagnotta, S., Cailleteau, L., et al. (2014) · Autophagy · doi:10.4161/auto.36182 · Cited by 422 · see citing works
SKP2 attenuates autophagy through Beclin1-ubiquitination and its inhibition reduces MERS-Coronavirus infection
Gassen, N. C., Niemeyer, D., Muth, D., Corman, V. M., Martinelli, S., Gassen, A., Hafner, K., Papies, J., Mösbauer, K., Zellner, A., et al. (2019) · Nature Communications · doi:10.1038/s41467-019-13659-4 · Cited by 356 · see citing works
Rubicon inhibits autophagy and accelerates hepatocyte apoptosis and lipid accumulation in nonalcoholic fatty liver disease in mice
Tanaka, S., Hikita, H., Tatsumi, T., Sakamori, R., Nozaki, Y., Sakane, S., Shiode, Y., Nakabori, T., Saito, Y., Hiramatsu, N., et al. (2016) · Hepatology · doi:10.1002/hep.28820 · Cited by 376 · see citing works
Self-citation
RETRACTED ARTICLE: Noncanonical autophagy inhibits the autoinflammatory, lupus-like response to dying cells
Martinez, J., Cunha, L. D., Park, S., Yang, M., Lu, Q., Orchard, R., Li, Q.-Z., Yan, M., Janke, L., Guy, C., et al. (2016) · Nature · doi:10.1038/nature17950 · Cited by 381 · see citing works
Retracted
The ULK1 complex mediates MTORC1 signaling to the autophagy initiation machinery via binding and phosphorylating ATG14
Park, J.-M., Jung, C. H., Seo, M., Otto, N. M., Grunwald, D., Kim, K. H., Moriarity, B., Kim, Y.-M., Starker, C., Nho, R. S., et al. (2016) · Autophagy · doi:10.1080/15548627.2016.1140293 · Cited by 341 · see citing works
LC3-Associated Phagocytosis in Myeloid Cells Promotes Tumor Immune Tolerance
Cunha, L. D., Yang, M., Carter, R., Guy, C., Harris, L., Crawford, J. C., Quarato, G., Boada-Romero, E., Kalkavan, H., Johnson, M. D. L., et al. (2018) · Cell · doi:10.1016/j.cell.2018.08.061 · Cited by 334 · see citing works
Autophagosome-Lysosome Fusion
Lőrincz, P., & Juhász, G. (2020) · Journal of Molecular Biology · doi:10.1016/j.jmb.2019.10.028 · Cited by 328 · see citing works
The clearance of dying cells: table for two
Green, D. R., Oguin, T. H., & Martinez, J. (2016) · Cell Death & Differentiation · doi:10.1038/cdd.2015.172 · Cited by 314 · see citing works
Autophagosome targeting and membrane curvature sensing by Barkor/Atg14(L)
Fan, W., Nassiri, A., & Zhong, Q. (2011) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1016472108 · Cited by 285 · see citing works
LC3-Associated Phagocytosis and Inflammation
Heckmann, B. L., Boada-Romero, E., Cunha, L. D., Magne, J., & Green, D. R. (2017) · Journal of Molecular Biology · doi:10.1016/j.jmb.2017.08.012 · Cited by 276 · see citing works
Molecular Mechanisms of Autophagy in the Cardiovascular System
Gatica, D., Chiong, M., Lavandero, S., & Klionsky, D. J. (2015) · Circulation Research · doi:10.1161/circresaha.114.303788 · Cited by 272 · see citing works
Rubicon controls endosome maturation as a Rab7 effector
Sun, Q., Westphal, W., Wong, K. N., Tan, I., & Zhong, Q. (2010) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1010554107 · Cited by 251 · see citing works
Regulation of autophagy by phosphatidylinositol 3‐phosphate
Burman, C., & Ktistakis, N. T. (2010) · FEBS Letters · doi:10.1016/j.febslet.2010.01.011 · Cited by 234 · see citing works
A Kinase-Independent Role for EGF Receptor in Autophagy Initiation
Tan, X., Thapa, N., Sun, Y., & Anderson, R. A. (2015) · Cell · doi:10.1016/j.cell.2014.12.006 · Cited by 223 · see citing works
Autophagy mediates pharmacological lifespan extension by spermidineand resveratrol
Morselli, E., Galluzzi, L., Kepp, O., Criollo, A., Maiuri, M. C., Tavernarakis, N., Madeo, F., & Kroemer, G. (2009) · Aging · doi:10.18632/aging.100110 · Cited by 213 · see citing works
Mycobacterium tuberculosis is protected from NADPH oxidase and LC3-associated phagocytosis by the LCP protein CpsA
Köster, S., Upadhyay, S., Chandra, P., Papavinasasundaram, K., Yang, G., Hassan, A., Grigsby, S. J., Mittal, E., Park, H. S., Jones, V., et al. (2017) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1707792114 · Cited by 208 · see citing works
Suppression of autophagic activity by Rubicon is a signature of aging
Nakamura, S., Oba, M., Suzuki, M., Takahashi, A., Yamamuro, T., Fujiwara, M., Ikenaka, K., Minami, S., Tabata, N., Yamamoto, K., et al. (2019) · Nature Communications · doi:10.1038/s41467-019-08729-6 · Cited by 205 · see citing works
Self-citation
Autophagy Regulation of Metabolism Is Required for CD8+ T Cell Anti-tumor Immunity
DeVorkin, L., Pavey, N., Carleton, G., Comber, A., Ho, C., Lim, J., McNamara, E., Huang, H., Kim, P., Zacharias, L. G., et al. (2019) · Cell Reports · doi:10.1016/j.celrep.2019.03.037 · Cited by 185 · see citing works
Self-citation
Beclin 1 interactome controls the crosstalk between apoptosis, autophagy and inflammasome activation: Impact on the aging process
Salminen, A., Kaarniranta, K., & Kauppinen, A. (2013) · Ageing Research Reviews · doi:10.1016/j.arr.2012.11.004 · Cited by 173 · see citing works
ULK1 phosphorylates Ser30 of BECN1 in association with ATG14 to stimulate autophagy induction
Park, J.-M., Seo, M., Jung, C. H., Grunwald, D., Stone, M., Otto, N. M., Toso, E., Ahn, Y., Kyba, M., Griffin, T. J., et al. (2018) · Autophagy · doi:10.1080/15548627.2017.1422851 · Cited by 168 · see citing works
ATP13A2 regulates mitochondrial bioenergetics through macroautophagy
Gusdon, A. M., Zhu, J., Van Houten, B., & Chu, C. T. (2012) · Neurobiology of Disease · doi:10.1016/j.nbd.2011.12.015 · Cited by 167 · see citing works
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 · see citing works
The RUN Domain of Rubicon Is Important for hVps34 Binding, Lipid Kinase Inhibition, and Autophagy Suppression
Sun, Q., Zhang, J., Fan, W., Wong, K. N., Ding, X., Chen, S., & Zhong, Q. (2011) · Journal of Biological Chemistry · doi:10.1074/jbc.m110.126425 · Cited by 153 · see citing works
NRBF2 regulates autophagy and prevents liver injury by modulating Atg14L-linked phosphatidylinositol-3 kinase III activity
Lu, J., He, L., Behrends, C., Araki, M., Araki, K., Jun Wang, Q., Catanzaro, J. M., Friedman, S. L., Zong, W.-X., Fiel, M. I., et al. (2014) · Nature Communications · doi:10.1038/ncomms4920 · Cited by 148 · see citing works
Casein kinase 1α: biological mechanisms and theranostic potential
Jiang, S., Zhang, M., Sun, J., & Yang, X. (2018) · Cell Communication and Signaling · doi:10.1186/s12964-018-0236-z · Cited by 130 · see citing works
Defects of Vps15 in skeletal muscles lead to autophagic vacuolar myopathy and lysosomal disease
Nemazanyy, I., Blaauw, B., Paolini, C., Caillaud, C., Protasi, F., Mueller, A., Proikas‐Cezanne, T., Russell, R. C., Guan, K., Nishino, I., et al. (2013) · EMBO Molecular Medicine · doi:10.1002/emmm.201202057 · Cited by 126 · see citing works
Atg38 is required for autophagy-specific phosphatidylinositol 3-kinase complex integrity
Araki, Y., Ku, W.-C., Akioka, M., May, A. I., Hayashi, Y., Arisaka, F., Ishihama, Y., & Ohsumi, Y. (2013) · Journal of Cell Biology · doi:10.1083/jcb.201304123 · Cited by 119 · see citing works
The class 3 PI3K coordinates autophagy and mitochondrial lipid catabolism by controlling nuclear receptor PPARα
Iershov, A., Nemazanyy, I., Alkhoury, C., Girard, M., Barth, E., Cagnard, N., Montagner, A., Chretien, D., Rugarli, E. I., Guillou, H., et al. (2019) · Nature Communications · doi:10.1038/s41467-019-09598-9 · Cited by 109 · see citing works
Two Rab2 Interactors Regulate Dense-Core Vesicle Maturation
Ailion, M., Hannemann, M., Dalton, S., Pappas, A., Watanabe, S., Hegermann, J., Liu, Q., Han, H.-F., Gu, M., Goulding, M. Q., et al. (2014) · Neuron · doi:10.1016/j.neuron.2014.02.017 · Cited by 86 · see citing works
Pathogenic role of BECN1/Beclin 1 in the development of amyotrophic lateral sclerosis
Nassif, M., Valenzuela, V., Rojas-Rivera, D., Vidal, R., Matus, S., Castillo, K., Fuentealba, Y., Kroemer, G., Levine, B., & Hetz, C. (2014) · Autophagy · doi:10.4161/auto.28784 · Cited by 100 · see citing works
Age-dependent loss of adipose Rubicon promotes metabolic disorders via excess autophagy
Yamamuro, T., Kawabata, T., Fukuhara, A., Saita, S., Nakamura, S., Takeshita, H., Fujiwara, M., Enokidani, Y., Yoshida, G., Tabata, K., et al. (2020) · Nature Communications · doi:10.1038/s41467-020-17985-w · Cited by 97 · see citing works
Self-citation
Rubicon: <scp>LC</scp>3‐associated phagocytosis and beyond
Wong, S., Sil, P., & Martinez, J. (2018) · The FEBS Journal · doi:10.1111/febs.14354 · Cited by 101 · see citing works
Beclin 1 mitigates motor and neuropathological deficits in genetic mouse models of Machado–Joseph disease
Nascimento-Ferreira, I., Nóbrega, C., Vasconcelos-Ferreira, A., Onofre, I., Albuquerque, D., Aveleira, C., Hirai, H., Déglon, N., & Pereira de Almeida, L. (2013) · Brain · doi:10.1093/brain/awt144 · Cited by 96 · see citing works
Crosstalk between apoptosis and autophagy signaling pathways
(2020) · International Review of Cell and Molecular Biology · doi:10.1016/bs.ircmb.2020.01.003 · Cited by 92 · see citing works
MTORC1-mediated NRBF2 phosphorylation functions as a switch for the class III PtdIns3K and autophagy
Ma, X., Zhang, S., He, L., Rong, Y., Brier, L. W., Sun, Q., Liu, R., Fan, W., Chen, S., Yue, Z., et al. (2017) · Autophagy · doi:10.1080/15548627.2016.1269988 · Cited by 92 · see citing works
Autophagy in Pulmonary Diseases
Nakahira, K., Pabon Porras, M. A., & Choi, A. M. K. (2016) · American Journal of Respiratory and Critical Care Medicine · doi:10.1164/rccm.201512-2468so · Cited by 78 · see citing works
mVps34 Deletion in Podocytes Causes Glomerulosclerosis by Disrupting Intracellular Vesicle Trafficking
Chen, J., Chen, M. X., Fogo, A. B., Harris, R. C., & Chen, J.-K. (2013) · Journal of the American Society of Nephrology · doi:10.1681/asn.2012010101 · Cited by 82 · see citing works
LC3-associated phagocytosis protects against inflammation and liver fibrosis via immunoreceptor inhibitory signaling
Wan, J., Weiss, E., Ben Mkaddem, S., Mabire, M., Choinier, P.-M., Picq, O., Thibault-Sogorb, T., Hegde, P., Pishvaie, D., Bens, M., et al. (2020) · Science Translational Medicine · doi:10.1126/scitranslmed.aaw8523 · Cited by 77 · see citing works
RUBCN/rubicon and EGFR regulate lysosomal degradative processes in the retinal pigment epithelium (RPE) of the eye
Muniz-Feliciano, L., Doggett, T. A., Zhou, Z., & Ferguson, T. A. (2017) · Autophagy · doi:10.1080/15548627.2017.1380124 · Cited by 73 · see citing works
Enhanced repair of UV-induced DNA damage by 1,25-dihydroxyvitamin D3 in skin is linked to pathways that control cellular energy
Rybchyn, M. S., De Silva, W. G. M., Sequeira, V. B., McCarthy, B. Y., Dilley, A. V., Dixon, K. M., Halliday, G. M., & Mason, R. S. (2018) · Journal of Investigative Dermatology · doi:10.1016/j.jid.2017.11.037 · Cited by 63 · see citing works
“Get the Balance Right”: Pathological Significance of Autophagy Perturbation in Neuromuscular Disorders
Castets, P., Frank, S., Sinnreich, M., & Rüegg, M. A. (2016) · Journal of Neuromuscular Diseases · doi:10.3233/jnd-160153 · Cited by 49 · see citing works
LC3-associated phagocytosis (LAP): a potentially influential mediator of efferocytosis-related tumor progression and aggressiveness
Asare, P. F., Roscioli, E., Hurtado, P. R., Tran, H. B., Mah, C. Y., & Hodge, S. (2020) · Frontiers in Oncology · doi:10.3389/fonc.2020.01298 · Cited by 50 · see citing works
Metabolic effects of RUBCN/Rubicon deficiency in kidney proximal tubular epithelial cells
Matsuda, J., Takahashi, A., Takabatake, Y., Sakai, S., Minami, S., Yamamoto, T., Fujimura, R., Namba-Hamano, T., Yonishi, H., Nakamura, J., et al. (2020) · Autophagy · doi:10.1080/15548627.2020.1712107 · Cited by 44 · see citing works
Self-citation

Transiently expressed ATG16L1 inhibits autophagosome biogenesis and aberrantly targets RAB11-positive recycling endosomes
Li, J., Chen, Z., Stang, M. T., & Gao, W. (2016) · Autophagy · doi:10.1080/15548627.2016.1256521 · Cited by 23 · see citing works
Analyzing Lysosomes in Live Cells
Pryor, P. R. (2012) · Methods in enzymology on CD-ROM/Methods in enzymology · doi:10.1016/b978-0-12-388448-0.00016-4 · Cited by 28 · see citing works
Centrosomal P4.1-associated protein (CPAP) positively regulates endocytic vesicular transport and lysosome targeting of EGFRPreprint
Gudi, R. R., Palanisamy, V., & Vasu, C. (2020) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2020.08.03.234690
Proximity Ligation In situ Assay is a Powerful Tool to Monitor Specific ATG Protein Interactions following Autophagy Induction
Gauthier, T., Claude‐Taupin, A., Delage-Mourroux, R., Boyer‐Guittaut, M., & Hervouet, É. (2015) · PLoS ONE · doi:10.1371/journal.pone.0128701 · Cited by 20 · see citing works
Atg41/Icy2 regulates autophagosome formation
Yao, Z., Delorme‐Axford, E., Backues, S. K., & Klionsky, D. J. (2015) · Autophagy · doi:10.1080/15548627.2015.1107692 · Cited by 90 · see citing works

Authors: Matsunaga, K., Saitoh, T., Tabata, K., Omori, H., Satoh, T., Kurotori, N., Maejima, I., Shirahama-Noda, K., Ichimura, T., Isobe, T., Akira, S., Noda, T., & Yoshimori, T.
Affiliations: The Graduate University for Advanced Studies, SOKENDAI (JP)
Immunology Frontier Research Center, The University of Osaka (JP)
Research Institute for Microbial Diseases, The University of Osaka (JP)
Tokyo Metropolitan University (JP)
Japan Science and Technology Agency (JP)
Corresponding author: Yoshimori, Tamotsu
ORCID: Matsunaga, Kohichi
Tabata, Keisuke
Satoh, Takashi
Maejima, Ikuko
Ichimura, Tohru
Isobe, Toshiaki
Akira, Shizuo
Noda, Takeshi
Yoshimori, Tamotsu
Venue: Nature Cell Biology
Publisher: Springer Science and Business Media LLC
Published: 2009-03-08
Volume: 11
Issue: 4
Pages: 385-396
ISSN: 1465-7392 (ISSN-L)
1476-4679
DOI: 10.1038/ncb1846
OpenAlex: W2064381459
Cited by: 1,235
References: 56
Citations by year: 2026: 44 · 2025: 54 · 2024: 64 · 2023: 59 · 2022: 73 · 2021: 90 · 2020: 79 · 2019: 84 · 2018: 56 · 2017: 77 · 2016: 85 · 2015: 59 · 2014: 80 · 2013: 91 · 2012: 90
FWCI: 53.71
Type: journal article
Language: en
Open access: closed
Licence: www.springer.com/tdm (tdm)
Locations: Nature Cell Biology (publishedVersion)
PubMed (publishedVersion)
Topics: Health Sciences › Medicine › Epidemiology › Autophagy in Disease and Therapy
Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular transport and secretion
Life Sciences › Biochemistry, Genetics and Molecular Biology › Physiology › Calcium signaling and nucleotide metabolism
Keywords: Beclin-1, ATG14L, Rubicon, autophagy, autophagosome formation, autophagosome maturation, class III phosphatidylinositol 3-kinase, UVRAG, endosomal trafficking, endosomes, lysosomes, isolation membrane, endoplasmic reticulum
MeSH terms: Beclin-1, Animals, Autophagy, Endocytosis, Humans, Membrane Proteins, Microtubule-Associated Proteins, Phagosomes, Protein Binding, Protein Processing, Post-Translational, Recombinant Fusion Proteins, Adaptor Proteins, Vesicular Transport, RNA, Small Interfering, Cell Line, Tumor, Multiprotein Complexes, Green Fluorescent Proteins, Apoptosis Regulatory Proteins, Mice

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Two Beclin 1-binding proteins, Atg14L and Rubicon, reciprocally regulate autophagy at different stages

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