Structural Basis for Sorting Mechanism of p62 in Selective Autophagy
Open accessAbstract
Impairment of autophagic degradation of the ubiquitin- and LC3-binding protein "p62" leads to the formation of cytoplasmic inclusion bodies. However, little is known about the sorting mechanism of p62 to autophagic degradation. Here we identified a motif of murine p62 consisting of 11 amino acids (Ser334-Ser344) containing conserved acidic and hydrophobic residues across species, as an LC3 recognition sequence (LRS). The crystal structure of the LC3-LRS complex at 1.56 angstroms resolution revealed interaction of Trp340 and Leu343 of p62 with different hydrophobic pockets on the ubiquitin fold of LC3. In vivo analyses demonstrated that p62 mutants lacking LC3 binding ability accumulated without entrapping into autophagosomes in the cytoplasm and subsequently formed ubiquitin-positive inclusion bodies as in autophagy-deficient cells. These results demonstrate that the intracellular level of p62 is tightly regulated by autophagy through the direct interaction of LC3 with p62 and reveal that selective turnover of p62 via autophagy controls inclusion body formation.
Integrity signals
Registry
Cites
Statistics
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?
SQSTM1 mutations affecting the UBA domain impair ubiquitin recognition, whereas mutations within the LIR domain impact LC3 recognition and substrate delivery to autophagosomes.
“SQSTM1 mutations affecting the UBA domain impair ubiquitin recognition [130], whereas mutations within the LIR domain impact LC3 recognition and substrate delivery to the autophagosomes [84,131].”
From Autophagy and ALS: mechanistic insights and therapeutic implications (2022) · cites this paper as [131]
Cites
[20] Processing of X-ray diffraction data collected in oscillation mode
Otwinowski, Z., & Minor, W. (1997) · Methods in Enzymology · doi:10.1016/s0076-6879(97)76066-x · Cited by 33,475 · see citing works
The PyMOL Molecular Graphics System
DeLano, W. L. (2002) · Medical Entomology and Zoology · Cited by 18,147 · see citing works
Refinement of Macromolecular Structures by the Maximum-Likelihood Method
Murshudov, G. N., Vagin, A. A., & Dodson, E. J. (1997) · Acta Crystallographica Section D Biological Crystallography · doi:10.1107/s0907444996012255 · Cited by 14,671 · see citing works
LC3, a mammalian homologue of yeast Apg8p, is localized in autophagosome membranes after processing.
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-citationTight control of gene expression in mammalian cells by tetracycline-responsive promoters.
Gossen, M., & Bujard, H. (1992) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.89.12.5547 · Cited by 4,943 · see citing works
MOLREP : an Automated Program for Molecular Replacement
Vagin, A. A., & Teplyakov, A. (1997) · Journal of Applied Crystallography · doi:10.1107/s0021889897006766 · Cited by 4,791 · see citing works
Pankiv, S., Clausen, T. H., Lamark, T., Brech, A., Bruun, J.-A., Outzen, H., Øvervatn, A., Bjørkøy, G., & Johansen, T. (2007) · Journal of Biological Chemistry · doi:10.1074/jbc.m702824200 · Cited by 4,578 · see citing works
Autophagy: process and functionPreprint
Mizushima, N. (2007) · Genes & Development · doi:10.1101/gad.1599207 · Cited by 3,967 · 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
Levine, B., & Klionsky, D. J. (2004) · Developmental Cell · doi:10.1016/s1534-5807(04)00099-1 · Cited by 3,671 · 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
Self-citationBjørkøy, 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
Impairment of starvation-induced and constitutive autophagy in <i>Atg7</i> -deficient mice
Komatsu, M., Waguri, S., Ueno, T., Iwata, J., Murata, S., Tanida, I., Ezaki, J., Mizushima, N., Ohsumi, Y., Uchiyama, Y., et al. (2005) · The Journal of Cell Biology · doi:10.1083/jcb.200412022 · Cited by 2,331 · see citing works
Self-citationHomeostatic 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
Self-citationXtalView/Xfit—A Versatile Program for Manipulating Atomic Coordinates and Electron Density
McRee, D. E. (1999) · Journal of Structural Biology · doi:10.1006/jsbi.1999.4094 · Cited by 2,096 · see citing works
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 2,064 · see citing works
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 1,701 · see citing works
LC3, GABARAP and GATE16 localize to autophagosomal membrane depending on form-II formation
Kabeya, Y., Mizushima, N., Yamamoto, A., Oshitani-Okamoto, S., Ohsumi, Y., & Yoshimori, T. (2004) · Journal of Cell Science · doi:10.1242/jcs.01131 · Cited by 1,394 · see citing works
Molecular dissection of autophagy: two ubiquitin-like systems
Ohsumi, Y. (2001) · Nature Reviews Molecular Cell Biology · doi:10.1038/35056522 · Cited by 1,240 · see citing works
Nakatogawa, H., Ichimura, Y., & Ohsumi, Y. (2007) · Cell · doi:10.1016/j.cell.2007.05.021 · Cited by 1,215 · see citing works
Self-citationThe Atg12-Atg5 Conjugate Has a Novel E3-like Activity for Protein Lipidation in Autophagy
Hanada, T., Noda, N. N., Satomi, Y., Ichimura, Y., Fujioka, Y., Takao, T., Inagaki, F., & Ohsumi, Y. (2007) · Journal of Biological Chemistry · doi:10.1074/jbc.c700195200 · Cited by 1,123 · see citing works
Self-citationKirisako, T., Ichimura, Y., Okada, H., Kabeya, Y., Mizushima, N., Yoshimori, T., Ohsumi, M., Takao, T., Noda, T., & Ohsumi, Y. (2000) · The Journal of Cell Biology · doi:10.1083/jcb.151.2.263 · Cited by 983 · see citing works
Self-citationFilimonenko, M., Stuffers, S., Raiborg, C., Yamamoto, A., Malerød, L., Fisher, E. M. C., Isaacs, A., Brech, A., Stenmark, H., & Simonsen, A. (2007) · The Journal of Cell Biology · doi:10.1083/jcb.200702115 · Cited by 626 · see citing works
p62 Is a Common Component of Cytoplasmic Inclusions in Protein Aggregation Diseases
Zatloukal, K., Stumptner, C., Fuchsbichler, A., Heid, H., Schnoelzer, M., Kenner, L., Kleinert, R., Prinz, M., Aguzzi, A., & Denk, H. (2002) · The American Journal of Pathology · doi:10.1016/s0002-9440(10)64369-6 · Cited by 624 · see citing works
ARP⧸wARP and Automatic Interpretation of Protein Electron Density Maps
Morris, R. J., Perrakis, A., & Lamzin, V. S. (2003) · Methods in enzymology on CD-ROM/Methods in enzymology · doi:10.1016/s0076-6879(03)74011-7 · Cited by 518 · see citing works
Kuma, A., Mizushima, N., Ishihara, N., & Ohsumi, Y. (2002) · Journal of Biological Chemistry · doi:10.1074/jbc.m111889200 · Cited by 441 · see citing works
Interaction Codes within the Family of Mammalian Phox and Bem1p Domain-containing Proteins
Lamark, T., Perander, M., Outzen, H., Kristiansen, K., Øvervatn, A., Michaelsen, E., Bjørkøy, G., & Johansen, T. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.m303221200 · Cited by 396 · see citing works
Molecular machinery of autophagosome formation in yeast, Saccharomyces cerevisiae
Suzuki, K., & Ohsumi, Y. (2007) · FEBS Letters · doi:10.1016/j.febslet.2007.01.096 · Cited by 394 · see citing works
Kuusisto, E., Salminen, A., & Alafuzoff, I. I. (2001) · Neuroreport · doi:10.1097/00001756-200107200-00009 · Cited by 347 · see citing works
Signal integration and diversification through the p62 scaffold protein
Moscat, J., Díaz-Meco, M. T., & WOOTEN, M. (2006) · Trends in Biochemical Sciences · doi:10.1016/j.tibs.2006.12.002 · Cited by 315 · see citing works
The CCP4 molecular-graphics project
Potterton, E. A., McNicholas, S. J., Krissinel, E., Cowtan, K. D., & Noble, M. E. M. (2002) · Acta Crystallographica Section D Biological Crystallography · doi:10.1107/s0907444902015391 · Cited by 220 · see citing works
Sou, Y., Tanida, I., Komatsu, M., Ueno, T., & Kominami, E. (2005) · Journal of Biological Chemistry · doi:10.1074/jbc.m505888200 · Cited by 205 · see citing works
Self-citationCell Signaling and Function Organized by PB1 Domain Interactions
Moscat, J., Díaz-Meco, M. T., Albert, A., & Campuzano, S. (2006) · Molecular Cell · doi:10.1016/j.molcel.2006.08.002 · Cited by 195 · see citing works
Sugawara, K., Suzuki, N. N., Fujioka, Y., Mizushima, N., Ohsumi, Y., & Inagaki, F. (2004) · Genes to Cells · doi:10.1111/j.1356-9597.2004.00750.x · Cited by 168 · see citing works
Sequestosome 1/p62 – More than just a scaffold
Seibenhener, M. L., Geetha, T., & Wooten, M. W. (2006) · FEBS Letters · doi:10.1016/j.febslet.2006.12.027 · Cited by 165 · see citing works
Constitutive autophagy: vital role in clearance of unfavorable proteins in neurons
Komatsu, M., Ueno, T., Waguri, S., Uchiyama, Y., Kominami, E., & Tanaka, K. (2007) · Cell Death and Differentiation · doi:10.1038/sj.cdd.4402120 · Cited by 161 · see citing works
Self-citationPaz, Y., Elazar, Z., & Fass, D. (2000) · Journal of Biological Chemistry · doi:10.1074/jbc.c000307200 · Cited by 146 · see citing works
Structure of GABARAP in Two Conformations
Coyle, J. E., Qamar, S., Rajashankar, K. R., & Nikolov, D. B. (2002) · Neuron · doi:10.1016/s0896-6273(01)00558-x · Cited by 142 · see citing works
Mallory body—A disease-associated type of sequestosome
Stumptner, C., Fuchsbichler, A., Heid, H., Zatloukal, K., & Denk, H. (2002) · Hepatology · doi:10.1053/jhep.2002.32674 · Cited by 133 · see citing works
Nakano, T., Nakaso, K., Ohama, E., & Nakashima, K. (2004) · Acta Neuropathologica · doi:10.1007/s00401-004-0821-7 · Cited by 78 · see citing works
Controlled gene expression with a reverse tetracycline-regulated retroviral vector (RTRV) system.
Watsuji, T., Okamoto, Y., Emi, N., Katsuoka, Y., & Hagiwara, M. (1997) · Biochemical and Biophysical Research Communications - BBRC · doi:10.1006/bbrc.1997.6705 · Cited by 69 · see citing works
Crystal structure of the GABAA‐receptor‐associated protein, GABARAP
Bavro, V. N., Solà, M., Bracher, A., Kneussel, M., Betz, H., & Weissenhorn, W. (2002) · EMBO Reports · doi:10.1093/embo-reports/kvf026 · Cited by 69 · see citing works
Two newly identified sites in the ubiquitin‐like protein Atg8 are essential for autophagy
Amar, N., Lustig, G., Ichimura, Y., Ohsumi, Y., & Elazar, Z. (2006) · EMBO Reports · doi:10.1038/sj.embor.7400698 · Cited by 52 · see citing works
Self-citationLee, G., Ogawa, K., & Drinkwater, N. R. (1995) · Europe PMC (PubMed Central) · Cited by 26 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Guidelines for the use and interpretation of assays for monitoring autophagy (3rd edition).
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
Guidelines for the use and interpretation of assays for monitoring autophagy
Klionsky, D. J., Abdalla, F. C., Abeliovich, H., Abraham, R. T., Acevedo-Arozena, A., Adeli, K., Agholme, L., Agnello, M., Agostinis, P., Aguirre-Ghiso, J. A., et al. (2012) · Autophagy · doi:10.4161/auto.19496 · Cited by 3,996 · see citing works
Klionsky, D. J., Abdel-Aziz, A. K., Abdelfatah, S., Abdellatif, M., Abdoli, A., Abel, S., Abeliovich, H., Abildgaard, M. H., Abudu, Y. P., Acevedo-Arozena, A., et al. (2021) · Autophagy · doi:10.1080/15548627.2020.1797280 · Cited by 2,622 · see citing works
Self-citationKomatsu, M., Kurokawa, H., Waguri, S., Taguchi, K., Kobayashi, A., Ichimura, Y., Sou, Y., Ueno, I., Sakamoto, A., Tong, K. I., et al. (2010) · Nature Cell Biology · doi:10.1038/ncb2021 · Cited by 2,422 · see citing works
Self-citationOxidative stress and autophagy: The clash between damage and metabolic needs
Filomeni, G., De Zio, D., & Cecconi, F. (2015) · Cell Death & Differentiation · doi:10.1038/cdd.2014.150 · Cited by 2,195 · see citing works
Selective autophagy mediated by autophagic adapter proteins
Johansen, T., & Lamark, T. (2011) · Autophagy · doi:10.4161/auto.7.3.14487 · Cited by 1,730 · see citing works
Dynamics and diversity in autophagy mechanisms: lessons from yeast
Nakatogawa, H., Suzuki, K., Kamada, Y., & Ohsumi, Y. (2009) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm2708 · Cited by 1,718 · see citing works
Jain, A., Lamark, T., Sjøttem, E., Bowitz Larsen, K., Atesoh Awuh, J., Øvervatn, A., McMahon, M., Hayes, J. D., & Johansen, T. (2010) · Journal of Biological Chemistry · doi:10.1074/jbc.m110.118976 · Cited by 1,472 · see citing works
The autophagosome: origins unknown, biogenesis complex
Lamb, C. A., Yoshimori, T., & Tooze, S. A. (2013) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm3696 · Cited by 1,307 · see citing works
Nix is a selective autophagy receptor for mitochondrial clearance
Novak, I., Kirkin, V., McEwan, D. G., Zhang, J., Wild, P., Rozenknop, A., Rogov, V., Löhr, F., Popovic, D., Occhipinti, A., et al. (2010) · The EMBO Reports · doi:10.1038/embor.2009.256 · Cited by 1,309 · see citing works
A Role for Ubiquitin in Selective Autophagy
Kirkin, V., McEwan, D. G., Novak, I., & Đikić, I. (2009) · Molecular Cell · doi:10.1016/j.molcel.2009.04.026 · Cited by 1,227 · see citing works
A Role for NBR1 in Autophagosomal Degradation of Ubiquitinated Substrates
Kirkin, V., Lamark, T., Sou, Y., Bjørkøy, G., Nunn, J. A. L., Bruun, J., Shvets, E., McEwan, D. G., Clausen, T. H., Wild, P. S., et al. (2009) · Molecular Cell · doi:10.1016/j.molcel.2009.01.020 · Cited by 1,156 · see citing works
Self-citationRogov, V., Dötsch, V., Johansen, T., & Kirkin, V. (2014) · Molecular Cell · doi:10.1016/j.molcel.2013.12.014 · Cited by 992 · see citing works
Autophagy—a key player in cellular and body metabolism
Kim, K. H., & Lee, M. (2014) · Nature Reviews Endocrinology · doi:10.1038/nrendo.2014.35 · Cited by 962 · see citing works
Liu, W. J., Ye, L., Huang, W. F., Guo, L. J., Xu, Z. G., Wu, H. L., Yang, C., & Liu, H. F. (2016) · Cellular & Molecular Biology Letters · doi:10.1186/s11658-016-0031-z · Cited by 921 · see citing works
Degradation of misfolded proteins in neurodegenerative diseases: Therapeutic targets and strategies
Ciechanover, A., & Kwon, Y. T. (2015) · Experimental & Molecular Medicine · doi:10.1038/emm.2014.117 · Cited by 898 · see citing works
The proteasome: overview of structure and functions
TANAKA, K. (2009) · Proceedings of the Japan Academy, Series B · doi:10.2183/pjab.85.12 · Cited by 862 · see citing works
Self-citationThe LIR motif – crucial for selective autophagy
Birgisdottir, Å. B., Lamark, T., & Johansen, T. (2013) · Journal of Cell Science · doi:10.1242/jcs.126128 · Cited by 871 · see citing works
Mitochondria-Anchored Receptor Atg32 Mediates Degradation of Mitochondria via Selective Autophagy
Okamoto, K., Kondo‐Okamoto, N., & Ohsumi, Y. (2009) · Developmental Cell · doi:10.1016/j.devcel.2009.06.013 · Cited by 867 · see citing works
Ubiquitination and selective autophagy
Shaid, S., Brandts, C. H., Serve, H., & Dikic, I. (2013) · Cell Death & Differentiation · doi:10.1038/cdd.2012.72 · Cited by 800 · see citing works
p62/ SQSTM 1 functions as a signaling hub and an autophagy adaptor
Katsuragi, Y., Ichimura, Y., & Komatsu, M. (2015) · FEBS Journal · doi:10.1111/febs.13540 · Cited by 795 · see citing works
Self-citationNarendra, D. P., Kane, L. A., Hauser, D. N., Fearnley, I. M., & Youle, R. J. (2010) · Autophagy · doi:10.4161/auto.6.8.13426 · Cited by 789 · see citing works
Nrf2, the Master Regulator of Anti-Oxidative Responses
Vomund, S., Schäfer, A., Parnham, M., Brüne, B., & Von Knethen, A. (2017) · International Journal of Molecular Sciences · doi:10.3390/ijms18122772 · Cited by 752 · see citing works
Selective Autophagy: ATG8 Family Proteins, LIR Motifs and Cargo Receptors
Johansen, T., & Lamark, T. (2019) · Journal of Molecular Biology · doi:10.1016/j.jmb.2019.07.016 · Cited by 700 · see citing works
Mammalian Autophagy: How Does It Work?
Bento, C. F., Renna, M., Ghislat, G., Puri, C., Ashkenazi, A., Vicinanza, M., Menzies, F. M., & Rubinsztein, D. C. (2016) · Annual Review of Biochemistry · doi:10.1146/annurev-biochem-060815-014556 · Cited by 692 · see citing works
Matsumoto, G., Wada, K., Okuno, M., Kurosawa, M., & Nukina, N. (2011) · Molecular Cell · doi:10.1016/j.molcel.2011.07.039 · Cited by 692 · see citing works
Deacetylation of Nuclear LC3 Drives Autophagy Initiation under Starvation
Huang, R., Xu, Y., Wan, W., Shou, X., Qian, J., You, Z., Liu, B., Chang, C., Zhou, T., Lippincott‐Schwartz, J., et al. (2015) · Molecular Cell · doi:10.1016/j.molcel.2014.12.013 · Cited by 679 · see citing works
Persistent activation of Nrf2 through p62 in hepatocellular carcinoma cells
Inami, Y., Waguri, S., Sakamoto, A., Kouno, T., Nakada, K., Hino, O., Watanabe, S., Ando, J., Iwadate, M., Yamamoto, M. P., et al. (2011) · The Journal of Cell Biology · doi:10.1083/jcb.201102031 · Cited by 602 · see citing works
Self-citationMechanisms of Selective Autophagy
Zaffagnini, G., & Martens, S. (2016) · Journal of Molecular Biology · doi:10.1016/j.jmb.2016.02.004 · Cited by 591 · see citing works
The Adaptor Protein p62/SQSTM1 Targets Invading Bacteria to the Autophagy Pathway
Zheng, Y. T., Shahnazari, S., Brech, A., Lamark, T., Johansen, T., & Brumell, J. H. (2009) · The Journal of Immunology · doi:10.4049/jimmunol.0900441 · Cited by 581 · see citing works
Atg8‐family interacting motif crucial for selective autophagy
Noda, N. N., Ohsumi, Y., & Inagaki, F. (2010) · FEBS Letters · doi:10.1016/j.febslet.2010.01.018 · Cited by 556 · see citing works
Atg8: an autophagy-related ubiquitin-like protein family.
Shpilka, T., Weidberg, H., Pietrokovski, S., & Elazar, Z. (2011) · Genome biology · doi:10.1186/gb-2011-12-7-226 · Cited by 543 · see citing works
“The motif in p62 responsible for binding Atg8, the LC3interacting region (LIR, also known as Atg8-interacting motif, AIM) [104,105], is common to other proteins that interact with Atg8 proteins, including Nbr1 [106], Atg3 [107], Nix [96] and the yeast cytoplasm-to-vacuole targeting receptor Atg19 [108].”
BackgroundCancer Chemoprevention Mechanisms Mediated Through the Keap1–Nrf2 Pathway
Hayes, J. D., McMahon, M. J., Chowdhry, S., & Dinkova‐Kostova, A. T. (2010) · Antioxidants and Redox Signaling · doi:10.1089/ars.2010.3221 · Cited by 540 · see citing works
A Diversity of Selective Autophagy Receptors Determines the Specificity of the Autophagy Pathway
Kirkin, V., & Rogov, V. V. (2019) · Molecular Cell · doi:10.1016/j.molcel.2019.09.005 · Cited by 524 · see citing works
Physiological significance of selective degradation of p62 by autophagy
Komatsu, M., & Ichimura, Y. (2010) · FEBS Letters · doi:10.1016/j.febslet.2010.02.017 · Cited by 516 · see citing works
Self-citationAggrephagy: Selective Disposal of Protein Aggregates by Macroautophagy
Lamark, T., & Johansen, T. (2012) · International Journal of Cell Biology · doi:10.1155/2012/736905 · Cited by 490 · see citing works
Amm, I., Sommer, T., & Wolf, D. H. (2013) · Biochimica et Biophysica Acta (BBA) - Molecular Cell Research · doi:10.1016/j.bbamcr.2013.06.031 · Cited by 493 · see citing works
Sou, Y., Waguri, S., Iwata, J.-I., Ueno, T., Fujimura, T., Hara, T., Sawada, N., Yamada, A., Mizushima, N., Uchiyama, Y., et al. (2008) · Molecular Biology of the Cell · doi:10.1091/mbc.e08-03-0309 · Cited by 475 · see citing works
Self-citationBiogenesis 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
Sandri, M. (2010) · FEBS Letters · doi:10.1016/j.febslet.2010.01.056 · Cited by 451 · see citing works
Smith, M. D., Harley, M. E., Kemp, A. J., Wills, J. C., Lee, M. W., Arends, M. J., von Kriegsheim, A., Behrends, C., & Wilkinson, S. (2017) · Developmental Cell · doi:10.1016/j.devcel.2017.11.024 · Cited by 443 · see citing works
A Small Molecule Inhibitor of Inducible Heat Shock Protein 70
Leu, J. I.-J., Pimkina, J. S., Frank, A. K., Murphy, M. E., & George, D. L. (2009) · Molecular Cell · doi:10.1016/j.molcel.2009.09.023 · Cited by 442 · see citing works
Graphene quantum dots as autophagy-inducing photodynamic agents
Marković, Z. M., Ristic, B. Z., Arsikin, K. M., Klisic, D., Harhaji-Trajkovic, L. M., Marković, B. M. T., Kepić, D., Kravic‐Stevovic, T., Jovanović, S., Milenkovic, M. M., et al. (2012) · Biomaterials · doi:10.1016/j.biomaterials.2012.06.060 · Cited by 441 · see citing works
Structural basis of target recognition by Atg8/LC3 during selective autophagy
Noda, N. N., Kumeta, H., Nakatogawa, H., Satoo, K., Adachi, W., Ishii, J., Fujioka, Y., Ohsumi, Y., & Inagaki, F. (2008) · Genes to Cells · doi:10.1111/j.1365-2443.2008.01238.x · Cited by 428 · see citing works
Crosstalk Between Mammalian Autophagy and the Ubiquitin-Proteasome System
Kocatürk, N. M., & Gözüaçık, D. (2018) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2018.00128 · Cited by 415 · see citing works
Receptor-mediated mitophagy in yeast and mammalian systems
Liu, L., Sakakibara, K., Chen, Q., & Okamoto, K. (2014) · Cell Research · doi:10.1038/cr.2014.75 · Cited by 421 · see citing works
p62 targeting to the autophagosome formation site requires self-oligomerization but not LC3 binding
Itakura, E., & Mizushima, N. (2011) · The Journal of Cell Biology · doi:10.1083/jcb.201009067 · Cited by 415 · see citing works
Autophagy in lysosomal storage disorders
Lieberman, A. P., Puertollano, R., Raben, N., Slaugenhaupt, S., Walkley, S. U., & Ballabio, A. (2012) · Autophagy · doi:10.4161/auto.19469 · Cited by 399 · see citing works
p62/SQSTM1 cooperates with Parkin for perinuclear clustering of depolarized mitochondria
Okatsu, K., Saisho, K., Shimanuki, M., Nakada, K., Shitara, H., Sou, Y., Kimura, M., Sato, S., Hattori, N., Komatsu, M., et al. (2010) · Genes to Cells · doi:10.1111/j.1365-2443.2010.01426.x · Cited by 397 · see citing works
“…degradation. p62 can interact with both ubiquitin and the autophagic machinery LC-3 (Bjorkoy et al. 2005; Komatsu et al. 2007; Pankiv et al. 2007; Ichimura et al. 2008; Noda et al. 2008; Shvets et al. 2008) and thus p62 is a plausible factor that links Parkin-catalyzed ubiquitylation with…”
BackgroundMethodInfluentialSelf-citationHamacher‐Brady, A., & Brady, N. R. (2015) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-015-2087-8 · Cited by 396 · see citing works
LC3-positive structures are prominent in autophagy-deficient cells
Runwal, G., Stamatakou, E., Siddiqi, F. H., Puri, C., Zhu, Y., & Rubinsztein, D. C. (2019) · Scientific Reports · doi:10.1038/s41598-019-46657-z · Cited by 413 · see citing works
Autophagy in acute kidney injury
Kaushal, G. P., & Shah, S. V. (2016) · Kidney International · doi:10.1016/j.kint.2015.11.021 · Cited by 389 · see citing works
Autophagy negatively regulates Wnt signalling by promoting Dishevelled degradation
Gao, C., Cao, W., Bao, L., Zuo, W., Xie, G., Cai, T., Fu, W., Zhang, J., Wu, W., Zhang, X., et al. (2010) · Nature Cell Biology · doi:10.1038/ncb2082 · Cited by 385 · see citing works
Satoo, K., Noda, N. N., Kumeta, H., Fujioka, Y., Mizushima, N., Ohsumi, Y., & Inagaki, F. (2009) · The EMBO Journal · doi:10.1038/emboj.2009.80 · Cited by 381 · see citing works
Autophagy in liver diseases: Time for translation?
Allaire, M., Rautou, P.-E., Codogno, P., & Lotersztajn, S. (2019) · Journal of Hepatology · doi:10.1016/j.jhep.2019.01.026 · Cited by 378 · see citing works
Sahani, M. H., Itakura, E., & Mizushima, N. (2014) · Autophagy · doi:10.4161/auto.27344 · Cited by 363 · see citing works
van der Veen, A. G., & Ploegh, H. L. (2012) · Annual Review of Biochemistry · doi:10.1146/annurev-biochem-093010-153308 · Cited by 364 · see citing works
p62 filaments capture and present ubiquitinated cargos for autophagy
Zaffagnini, G., Savova, A., Danieli, A., Romanov, J., Tremel, S., Ebner, M., Peterbauer, T., Sztacho, M., Trapannone, R., Tarafder, A. K., et al. (2018) · The EMBO Journal · doi:10.15252/embj.201798308 · Cited by 361 · see citing works
Noda, N. N., & Inagaki, F. (2015) · Annual Review of Biophysics · doi:10.1146/annurev-biophys-060414-034248 · Cited by 358 · see citing works
Svenning, S., Lamark, T., Krause, K., & Johansen, T. (2011) · Autophagy · doi:10.4161/auto.7.9.16389 · Cited by 357 · see citing works
Autophagy and the ubiquitin-proteasome system: Collaborators in neuroprotection
Nedelsky, N. B., Todd, P. K., & Taylor, J. P. (2008) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2008.10.002 · Cited by 351 · see citing works
Raben, N., Hill, V., Shea, L., Takikita, S., Baum, R., Mizushima, N., Ralston, E., & Plotz, P. (2008) · Human Molecular Genetics · doi:10.1093/hmg/ddn292 · Cited by 352 · see citing works
FIP200 Claw Domain Binding to p62 Promotes Autophagosome Formation at Ubiquitin Condensates
Turco, E., Witt, M., Abert, C., Bock-Bierbaum, T., Su, M.-Y., Trapannone, R., Sztacho, M., Danieli, A., Shi, X., Zaffagnini, G., et al. (2019) · Molecular Cell · doi:10.1016/j.molcel.2019.01.035 · Cited by 333 · see citing works
Rojansky, R. B., Cha, M.-Y., & Chan, D. C. (2016) · eLife · doi:10.7554/elife.17896 · Cited by 337 · see citing works
von Muhlinen, N., Akutsu, M., Ravenhill, B. J., Foeglein, Á., Bloor, S., Rutherford, T. J., Freund, S. M. V., Komander, D., & Randow, F. (2012) · Molecular Cell · doi:10.1016/j.molcel.2012.08.024 · Cited by 332 · see citing works
Lim, J., Lachenmayer, M. L., Wu, S., Liu, W., Kundu, M., Wang, R., Komatsu, M., Oh, Y. J., Zhao, Y., & Yue, Z. (2015) · PLoS Genetics · doi:10.1371/journal.pgen.1004987 · Cited by 323 · see citing works
Self-citationAutolysosomal β‐catenin degradation regulates Wnt‐autophagy‐p62 crosstalk
Petherick, K. J., Williams, A. C., Lane, J. D., Ordóñez‐Morán, P., Huelsken, J., Collard, T. J., Smartt, H. J. M., Batson, J., Malik, K. T. A., Paraskeva, C., et al. (2013) · The EMBO Journal · doi:10.1038/emboj.2013.123 · Cited by 318 · see citing works
Cosín‐Roger, J., Simmen, S., Melhem, H., Atrott, K., Frey-Wagner, I. M., Hausmann, M., de Vallière, C., Spalinger, M. R., Spielmann, P., Wenger, R. H., et al. (2017) · Nature Communications · doi:10.1038/s41467-017-00213-3 · Cited by 309 · see citing works
Ponpuak, M., Davis, A. S., Roberts, E. A., Delgado, M. A., Dinkins, C., Zhao, Z., Virgin, H. W., Kyei, G. B., Johansen, T., Vergne, I., et al. (2010) · Immunity · doi:10.1016/j.immuni.2010.02.009 · Cited by 308 · see citing works
p62/SQSTM1/A170: Physiology and pathology
Komatsu, M., Kageyama, S., & Ichimura, Y. (2012) · Pharmacological Research · doi:10.1016/j.phrs.2012.07.004 · Cited by 301 · see citing works
Self-citationRogov, V. V., SUZUKI, H., Marinković, M., Lang, V., Kato, R., Kawasaki, M., Buljubašić, M., Šprung, M., Rogova, N. Y., Soichi Wakatsuki, A., et al. (2017) · Scientific Reports · doi:10.1038/s41598-017-01258-6 · Cited by 299 · see citing works
Kageyama, S., Gudmundsson, S. R., Sou, Y., Ichimura, Y., Tamura, N., Kazuno, S., Ueno, T., Miura, Y., Noshiro, D., Abe, M., et al. (2021) · Nature Communications · doi:10.1038/s41467-020-20185-1 · Cited by 290 · see citing works
Self-citationATG8 Family Proteins Act as Scaffolds for Assembly of the ULK Complex
Alemu, E. A., Lamark, T., Torgersen, K. M., Birgisdottir, Å. B., Larsen, K. B., Jain, A., Olsvik, H. L., Øvervatn, A., Kirkin, V., & Johansen, T. (2012) · Journal of Biological Chemistry · doi:10.1074/jbc.m112.378109 · Cited by 288 · see citing works
HUWE1 E3 ligase promotes PINK1/PARKIN-independent mitophagy by regulating AMBRA1 activation via IKKα
Rita, A. D., Peschiaroli, A., D’Acunzo, P., Strobbe, D., Hu, Z., Gruber, J., Nygaard, M. M., Lambrughi, M., Melino, G., Papaleo, E., et al. (2018) · Nature Communications · doi:10.1038/s41467-018-05722-3 · Cited by 287 · see citing works
<i>SQSTM1</i> mutations in frontotemporal lobar degeneration and amyotrophic lateral sclerosis
Rubino, E., Rainero, I., Chiò, A., Rogaeva, E., Galimberti, D., Fenoglio, P., Grinberg, Y., Isaia, G., Calvo, A., Gentile, S., et al. (2012) · Neurology · doi:10.1212/wnl.0b013e31826e25df · Cited by 286 · see citing works
p62/SQSTM1 – steering the cell through health and disease
Sánchez‐Martín, P., & Komatsu, M. (2018) · Journal of Cell Science · doi:10.1242/jcs.222836 · Cited by 280 · see citing works
Self-citationDynamic regulation of macroautophagy by distinctive ubiquitin-like proteins
Klionsky, D. J., & Schulman, B. A. (2014) · Nature Structural & Molecular Biology · doi:10.1038/nsmb.2787 · Cited by 274 · see citing works
Liu, Y., Soto-Burgos, J., Deng, Y., Srivastava, R., Howell, S. H., & Bassham, D. C. (2012) · The Plant Cell · doi:10.1105/tpc.112.101535 · Cited by 274 · see citing works
Wurzer, B., Zaffagnini, G., Fracchiolla, D., Turco, E., Abert, C., Romanov, J., & Martens, S. (2015) · eLife · doi:10.7554/elife.08941 · Cited by 271 · see citing works
Nrf2 promotes the development of fibrosis and tumorigenesis in mice with defective hepatic autophagy
Ni, H.-M., Woolbright, B. L., Williams, J., Copple, B., Cui, W., Luyendyk, J. P., Jaeschke, H., & Ding, W.-X. (2014) · Journal of Hepatology · doi:10.1016/j.jhep.2014.04.043 · Cited by 270 · see citing works
Pankiv, S., Lamark, T., Bruun, J., Øvervatn, A., Bjørkøy, G., & Johansen, T. (2009) · Journal of Biological Chemistry · doi:10.1074/jbc.m109.039925 · Cited by 266 · see citing works
p62- and ubiquitin-dependent stress-induced autophagy of the mammalian 26S proteasome
Cohen‐Kaplan, V., Livneh, I., Avni, N., Fabre, B., Ziv, T., Kwon, Y. T., & Ciechanover, A. J. (2016) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1615455113 · Cited by 257 · see citing works
Wei, H., Liu, L., & Chen, Q. (2015) · Biochimica et Biophysica Acta (BBA) - Molecular Cell Research · doi:10.1016/j.bbamcr.2015.03.013 · Cited by 256 · see citing works
The LC3 interactome at a glance
Wild, P. S., McEwan, D. G., & Đikić, I. (2013) · Journal of Cell Science · doi:10.1242/jcs.140426 · Cited by 250 · see citing works
Autophagy in Spinal Cord Motor Neurons in Sporadic Amyotrophic Lateral Sclerosis
Sasaki, S. (2011) · Journal of Neuropathology & Experimental Neurology · doi:10.1097/nen.0b013e3182160690 · Cited by 249 · see citing works
Mitochondrial BCL‐2 inhibits AMBRA1‐induced autophagy
Strappazzon, F., Rudan, M. V., Campello, S., Nazio, F., Florenzano, F., Fimia, G. M., Piacentini, M., Levine, B., & Cecconi, F. (2011) · The EMBO Journal · doi:10.1038/emboj.2011.49 · Cited by 246 · see citing works
Selective degradation of p62 by autophagy
Ichimura, Y., & Komatsu, M. (2010) · Seminars in Immunopathology · doi:10.1007/s00281-010-0220-1 · Cited by 242 · see citing works
Self-citationAutophagy in bone homeostasis and the onset of osteoporosis
Yin, X., Zhou, C., Li, J., Liu, R., Shi, B., Yuan, Q., & Zou, S. (2019) · Bone Research · doi:10.1038/s41413-019-0058-7 · Cited by 235 · see citing works
Aging: Central role for autophagy and the lysosomal degradative system
Rajawat, Y. S., Hilioti, Z., & Bossis, I. (2009) · Ageing Research Reviews · doi:10.1016/j.arr.2009.05.001 · Cited by 247 · see citing works
p62/ SQSTM 1: ‘Jack of all trades’ in health and cancer
Sánchez‐Martín, P., Saito, T., & Komatsu, M. (2018) · FEBS Journal · doi:10.1111/febs.14712 · Cited by 242 · see citing works
Self-citationKuma, A., & Mizushima, N. (2010) · Seminars in Cell & Developmental Biology · doi:10.1016/j.semcdb.2010.03.002 · Cited by 237 · see citing works
When autophagy meets cancer through p62/SQSTM1.
Puissant, A., Fenouille, N., & Auberger, P. (2012) · Europe PMC (PubMed Central) · Cited by 236 · see citing works
Turco, E., Savova, A., Gere, F., Ferrari, L., Romanov, J., Schuschnig, M., & Martens, S. (2021) · Nature Communications · doi:10.1038/s41467-021-25572-w · Cited by 235 · see citing works
The Spectrum of Achalasia: Lessons From Studies of Pathophysiology and High-Resolution Manometry
Kahrilas, P. J., & Boeckxstaens, G. E. (2013) · Gastroenterology · doi:10.1053/j.gastro.2013.08.038 · Cited by 234 · see citing works
Dafinca, R., Scaber, J., Ababneh, N. A., Lalic, T., Weir, G. A., Christian, H., Vowles, J., Douglas, A. G. L., Fletcher-Jones, A., Browne, C., et al. (2016) · Stem Cells · doi:10.1002/stem.2388 · Cited by 234 · see citing works
Autophagic Regulation of p62 is Critical for Cancer Therapy
Islam, M. A., Sooro, M. A., & Zhang, P. (2018) · International Journal of Molecular Sciences · doi:10.3390/ijms19051405 · Cited by 234 · see citing works
LC3/GABARAPs drive ubiquitin-independent recruitment of Optineurin and NDP52 to amplify mitophagy
Padman, B. S., Nguyen, T. N., Uoselis, L., Skulsuppaisarn, M., Nguyen, L. K., & Lazarou, M. (2019) · Nature Communications · doi:10.1038/s41467-019-08335-6 · Cited by 234 · see citing works
Wang, Y., Zhang, N., Zhang, L., Li, R., Fu, W., Ma, K., Li, X., Wang, L., Wang, J., Zhang, H., et al. (2016) · Molecular Cell · doi:10.1016/j.molcel.2016.05.027 · Cited by 232 · see citing works
Autophagy signal transduction by ATG proteins: from hierarchies to networks
Wesselborg, S., & Stork, B. (2015) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-015-2034-8 · Cited by 231 · see citing works
Autophagy Signaling Through Reactive Oxygen Species
Huang, J., Lam, G. Y., & Brumell, J. H. (2010) · Antioxidants and Redox Signaling · doi:10.1089/ars.2010.3554 · Cited by 226 · see citing works
- Authors
- Ichimura, Y., Kumanomidou, T., Sou, Y.-S., Mizushima, T., Ezaki, J., Ueno, T., Kominami, E., Yamane, T., Tanaka, K., & Komatsu, M.
- Affiliations
- Juntendo University (JP)
- Nagoya University (JP)
- Tokyo Metropolitan Institute of Medical Science (JP)
- Corresponding author
- Komatsu, Masaaki
- ORCID
- Venue
- Journal of Biological Chemistry
- Publisher
- Elsevier BV
- Published
- 2008-08
- Volume
- 283
- Issue
- 33
- Pages
- 22847-22857
- ISSN
- 0021-9258 (ISSN-L)
- OpenAlex
- W2125123150
- Semantic Scholar
- 35145bb1648360bcd497256c99d185ca87c08d94
- Cited by
- 803
- References
- 44
- Citations by year
- 2026: 25 · 2025: 35 · 2024: 39 · 2023: 50 · 2022: 36 · 2021: 49 · 2020: 47 · 2019: 55 · 2018: 43 · 2017: 44 · 2016: 55 · 2015: 38 · 2014: 54 · 2013: 49 · 2012: 60
- FWCI
- 31.03
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Biological Chemistry (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Epidemiology › Autophagy in Disease and Therapy
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Ubiquitin and proteasome pathways
- Health Sciences › Medicine › Neurology › Amyotrophic Lateral Sclerosis Research
- Keywords
- p62, selective autophagy, crystal structure, hydrophobic pocket, protein turnover
- MeSH terms
- Sequestosome-1 Protein, Autophagy, Binding Sites, Carrier Proteins, Lysosomes, Microtubule-Associated Proteins, Recombinant Fusion Proteins, Vacuoles, Sequence Deletion, Adaptor Proteins, Signal Transducing, Maltose-Binding Proteins
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