Cited by 932Heat shock proteins researchAutophagy in Disease and TherapyGenetic Neurodegenerative Diseases

The DOI matches its Crossref record; 57 of the 57 references it cites were found in a registry or an index.

Misfolded proteins partition between two distinct quality control compartments

Open access

Kaganovich, Daniel, Kopito, Ron, Frydman, Judith·2008·Nature

Open this paper in CoChat — free account

Abstract

The accumulation of misfolded proteins in intracellular amyloid inclusions, typical of many neurodegenerative disorders including Huntington's and prion disease, is thought to occur after failure of the cellular protein quality control mechanisms. Here we examine the formation of misfolded protein inclusions in the eukaryotic cytosol of yeast and mammalian cell culture models. We identify two intracellular compartments for the sequestration of misfolded cytosolic proteins. Partition of quality control substrates to either compartment seems to depend on their ubiquitination status and aggregation state. Soluble ubiquitinated misfolded proteins accumulate in a juxtanuclear compartment where proteasomes are concentrated. In contrast, terminally aggregated proteins are sequestered in a perivacuolar inclusion. Notably, disease-associated Huntingtin and prion proteins are preferentially directed to the perivacuolar compartment. Enhancing ubiquitination of a prion protein suffices to promote its delivery to the juxtanuclear inclusion. Our findings provide a framework for understanding the preferential accumulation of amyloidogenic proteins in inclusions linked to human disease.

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

Integrity signals

Registry

Crossref · 10.1038/nature07195

Cites

57 of 57 references verified0 citation errors · 0 not checkable

Statistics

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

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?

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

1 retracted

RETRACTED ARTICLE: A specific amyloid-β protein assembly in the brain impairs memory
Lesné, S., Koh, M. T., Kotilinek, L., Kayed, R., Glabe, C. G., Yang, A., Gallagher, M., & Ashe, K. H. (2006) · Nature · doi:10.1038/nature04533 · Cited by 2,769
Retracted
Protein Misfolding, Functional Amyloid, and Human Disease
Chiti, F., & Dobson, C. M. (2006) · Annual Review of Biochemistry · doi:10.1146/annurev.biochem.75.101304.123901 · Cited by 6,497
Methods in Yeast Genetics
Jacob, H. (1988) · Bioelectrochemistry and Bioenergetics · doi:10.1016/0302-4598(88)80052-7 · Cited by 4,911
Improved monomeric red, orange and yellow fluorescent proteins derived from Discosoma sp. red fluorescent protein
Shaner, N. C., Campbell, R. E., Steinbach, P. A., Giepmans, B. N. G., Palmer, A. E., & Tsien, R. Y. (2004) · Nature Biotechnology · doi:10.1038/nbt1037 · Cited by 4,619
p62/SQSTM1 Binds Directly to Atg8/LC3 to Facilitate Degradation of Ubiquitinated Protein Aggregates by Autophagy
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
Functional Characterization of the S. cerevisiae Genome by Gene Deletion and Parallel Analysis
Winzeler, E. A., Shoemaker, D. D., Astromoff, A., Liang, H., Anderson, K., Andre, B., Bangham, R., Benito, R., Boeke, J. D., Bussey, H., et al. (1999) · Science · doi:10.1126/science.285.5429.901 · Cited by 3,953
Adapting Proteostasis for Disease Intervention
Balch, W. E., Morimoto, R. I., Dillin, A., & Kelly, J. W. (2008) · Science · doi:10.1126/science.1141448 · Cited by 2,495
Inherent toxicity of aggregates implies a common mechanism for protein misfolding diseases
Bucciantini, M., Giannoni, E., Chiti, F., Baroni, F., Formigli, L., Zurdo, J., Taddei, N., Ramponi, G., Dobson, C. M., & Stefani, M. (2002) · Nature · doi:10.1038/416507a · Cited by 2,434
Impairment of the Ubiquitin-Proteasome System by Protein Aggregation
Bence, N., Sampat, R. M., & Kopito, R. R. (2001) · Science · doi:10.1126/science.292.5521.1552 · Cited by 2,209
Self-citation
Inclusion body formation reduces levels of mutant huntingtin and the risk of neuronal death
Arrasate, M., Mitra, S., Schweitzer, E. S., Segal, M. R., & Finkbeiner, S. (2004) · Nature · doi:10.1038/nature02998 · Cited by 1,979

Flagged first, then by citations

Show all 57 references

Sorted by citations

Items 201–300 of 925

RNA-binding and prion domains: the Yin and Yang of phase separation
Lorenzo-Gotor, N., Armaos, A., Calloni, G., Torrent, M., Vabulas, R. M., de Groot, N. S., & Tartaglia, G. G. (2020) · Nucleic Acids Research · doi:10.1093/nar/gkaa681 · Cited by 82
A nuclear-based quality control pathway for non-imported mitochondrial proteins
Shakya, V. P. S., Barbeau, W. A., Xiao, T., Knutson, C. S., Schuler, M.-H., & Hughes, A. L. (2021) · eLife · doi:10.7554/elife.61230 · Cited by 86
MitoStores: chaperone‐controlled protein granules store mitochondrial precursors in the cytosol
Krämer, L., Dalheimer, N., Räschle, M., Štorchová, Z., Pielage, J., Boos, F., & Herrmann, J. M. (2023) · The EMBO Journal · doi:10.15252/embj.2022112309 · Cited by 81
Of the atypical PKCs, Par-4 and p62: recent understandings of the biology and pathology of a PB1-dominated complex
Moscat, J., Díaz-Meco, M. T., & Wooten, M. W. (2009) · Cell Death and Differentiation · doi:10.1038/cdd.2009.119 · Cited by 86
Neurodegenerative diseases: Lessons from genome‐wide screens in small model organisms
van Ham, T. J., Breitling, R., Swertz, M. A., & Nollen, E. A. A. (2009) · EMBO Molecular Medicine · doi:10.1002/emmm.200900051 · Cited by 82
Segregation of Protein Aggregates Involves Actin and the Polarity Machinery
Liu, B., Larsson, L., Franssens, V., Hao, X., Hill, S. M., Andersson, V., Höglund, D., Song, J. M., Yang, X., Öling, D., et al. (2011) · Cell · doi:10.1016/j.cell.2011.11.018 · Cited by 81
Virus-Induced Chaperone-Enriched (VICE) Domains Function as Nuclear Protein Quality Control Centers during HSV-1 Infection
Livingston, C. M., Ifrim, M. F., Cowan, A. E., & Weller, S. K. (2009) · PLoS Pathogens · doi:10.1371/journal.ppat.1000619 · Cited by 81
Protein Quality Control in Health and DiseasePreprint
Dubnikov, T., Ben‐Gedalya, T., & Cohen, E. (2016) · Cold Spring Harbor Perspectives in Biology · doi:10.1101/cshperspect.a023523 · Cited by 82
The heat shock response in neurons and astroglia and its role in neurodegenerative diseases
Gil, R. S., Ooi, L., Yerbury, J. J., & Ecroyd, H. W. (2017) · Molecular Neurodegeneration · doi:10.1186/s13024-017-0208-6 · Cited by 80
Control of the structural landscape and neuronal proteotoxicity of mutant Huntingtin by domains flanking the polyQ tract
Shen, K., Calamini, B., Fauerbach, J. A., Ma, B., Shahmoradian, S. H., Lachapel, I. L. S., Chiu, W., Lo, D. C., & Frydman, J. (2016) · eLife · doi:10.7554/elife.18065 · Cited by 77
Self-citation
Protein Quality Control in Neurodegenerative Disease
Gestwicki, J. E., & Garza, D. (2012) · Progress in molecular biology and translational science · doi:10.1016/b978-0-12-385883-2.00003-5 · Cited by 80
Huntington’s Disease Pathogenesis Is Modified In Vivo by Alfy/Wdfy3 and Selective Macroautophagy
Fox, L. M., Kim, K., Johnson, C. W., Chen, S., Croce, K. R., Victor, M. B., Eenjes, E., Bosco, J. R., Randolph, L. K., Dragatsis, I., et al. (2020) · Neuron · doi:10.1016/j.neuron.2019.12.003 · Cited by 76
Role of asymmetric cell division in lifespan control in Saccharomyces cerevisiae
Higuchi‐Sanabria, R., Pernice, W. M., Vevea, J., Wolken, D. M. A., Boldogh, I. R., & Pon, L. A. (2014) · FEMS Yeast Research · doi:10.1111/1567-1364.12216 · Cited by 82
Spatial sequestration and detoxification of Huntingtin by the ribosome quality control complex
Yang, J., Hao, X., Cao, X., Liu, B., & Nyström, T. (2016) · eLife · doi:10.7554/elife.11792 · Cited by 77
Protein Quality Control Degradation in the Nucleus
Enam, C., Geffen, Y., Ravid, T., & Gardner, R. G. (2018) · Annual Review of Biochemistry · doi:10.1146/annurev-biochem-062917-012730 · Cited by 75
Protein assembly systems in natural and synthetic biology
Chiesa, G., Kiriakov, S., & Khalil, A. S. (2020) · BMC Biology · doi:10.1186/s12915-020-0751-4 · Cited by 76
The Type II Hsp40 Sis1 Cooperates with Hsp70 and the E3 Ligase Ubr1 to Promote Degradation of Terminally Misfolded Cytosolic Protein
Summers, D. W., Wolfe, K. J., Ren, H. Y., & Cyr, D. (2013) · PLoS ONE · doi:10.1371/journal.pone.0052099 · Cited by 75
The metazoan protein disaggregase and amyloid depolymerase system
Torrente, M. P., & Shorter, J. (2013) · Prion · doi:10.4161/pri.27531 · Cited by 75
Prion Induction by the Short-Lived, Stress-Induced Protein Lsb2 Is Regulated by Ubiquitination and Association with the Actin Cytoskeleton
Chernova, T. A., Romanyuk, A. V., Karpova, T., Shanks, J. R., Ali, M., Moffatt, N., Howie, R. L., O'Dell, A., McNally, J. G., Liebman, S. W., et al. (2011) · Molecular Cell · doi:10.1016/j.molcel.2011.07.001 · Cited by 76
Arabidopsis RTNLB1 and RTNLB2 Reticulon-Like Proteins Regulate Intracellular Trafficking and Activity of the FLS2 Immune Receptor
Lee, H. Y., Bowen, C. H., Popescu, G. V., Kang, H.-G., Kato, N., Ma, S., Dinesh‐Kumar, S. P., Snyder, M. P., & Popescu, S. C. (2011) · The Plant Cell · doi:10.1105/tpc.111.089656 · Cited by 75
High and stable ATP levels prevent aberrant intracellular protein aggregation in yeast
Takaine, M., Imamura, H., & Yoshida, S. (2022) · eLife · doi:10.7554/elife.67659 · Cited by 76
Aging and the aggregating proteome
David, D. C. (2012) · Frontiers in Genetics · doi:10.3389/fgene.2012.00247 · Cited by 76
Biochemical, Cell Biological, and Genetic Assays to Analyze Amyloid and Prion Aggregation in Yeast
Alberti, S., Halfmann, R., & Lindquist, S. L. (2010) · Methods in enzymology on CD-ROM/Methods in enzymology · doi:10.1016/s0076-6879(10)70030-6 · Cited by 74
A prion-like domain in Hsp42 drives chaperone-facilitated aggregation of misfolded proteins
Groušl, T., Ungelenk, S., Miller, S. B. M., Ho, C.-T., Khokhrina, M., Mayer, M. P., Bukau, B., & Mogk, A. (2018) · The Journal of Cell Biology · doi:10.1083/jcb.201708116 · Cited by 72
Interplay of Proteostasis Capacity and Protein Aggregation: Implications for Cellular Function and Disease
Hipp, M. S., & Hartl, F. U. (2024) · Journal of Molecular Biology · doi:10.1016/j.jmb.2024.168615 · Cited by 77
A Network of Ubiquitin Ligases Is Important for the Dynamics of Misfolded Protein Aggregates in Yeast
Theodoraki, M. A., Nillegoda, N. B., Saini, J., & Caplan, A. J. (2012) · Journal of Biological Chemistry · doi:10.1074/jbc.m112.341164 · Cited by 72
A dual‐functional BODIPY‐based molecular rotor probe reveals different viscosity of protein aggregates in live cells
Shen, B., Jung, K. H., Ye, S., Hoelzel, C. A., Wolstenholme, C. H., Huang, H., Liu, Y., & Zhang, X. (2022) · Aggregate · doi:10.1002/agt2.301 · Cited by 71
Prediction of the aggregation propensity of proteins from the primary sequence: Aggregation properties of proteomes
Castillo, V., Graña‐Montes, R., Sabaté, R., & Ventura, S. (2011) · Biotechnology Journal · doi:10.1002/biot.201000331 · Cited by 73
Sti1 Regulation of Hsp70 and Hsp90 Is Critical for Curing of Saccharomyces cerevisiae [ PSI + ] Prions by Hsp104
Reidy, M. J., & Masison, D. C. (2010) · Molecular and Cellular Biology · doi:10.1128/mcb.01292-09 · Cited by 71
The genetic basis of aneuploidy tolerance in wild yeast
Hose, J., Escalante, L. E., Clowers, K. J., Dutcher, H. A., Robinson, D., Bouriakov, V., Coon, J. J., Shishkova, E., & Gasch, A. P. (2020) · eLife · doi:10.7554/elife.52063 · Cited by 72
Coordinated Hsp110 and Hsp104 Activities Power Protein Disaggregation in Saccharomyces cerevisiae
Kaimal, J. M., Kandasamy, G., Gasser, F., & Andréasson, C. (2017) · Molecular and Cellular Biology · doi:10.1128/mcb.00027-17 · Cited by 70
Autophagic clearance of proteasomes in yeast requires the conserved sorting nexin Snx4
Nemec, A. A., Howell, L. A., Peterson, A. K., Murray, M. A., & Tomko, R. J. (2017) · Journal of Biological Chemistry · doi:10.1074/jbc.m117.817999 · Cited by 72
Prions, Chaperones, and Proteostasis in YeastPreprint
Chernova, T. A., Wilkinson, K. D., & Chernoff, Y. O. (2016) · Cold Spring Harbor Perspectives in Biology · doi:10.1101/cshperspect.a023663 · Cited by 70
Nervous yeast: modeling neurotoxic cell death
Braun, R. J., Büttner, S., Ring, J., Kroemer, G., & Madeo, F. (2009) · Trends in Biochemical Sciences · doi:10.1016/j.tibs.2009.10.005 · Cited by 71
Inefficient Translocation of Preproinsulin Contributes to Pancreatic β Cell Failure and Late-onset Diabetes
Guo, H., Xiong, Y., Witkowski, P., Cui, J., Wang, L.-J., Sun, J., Lara‐Lemus, R., Haataja, L., Hutchison, K., Shan, S., et al. (2014) · Journal of Biological Chemistry · doi:10.1074/jbc.m114.562355 · Cited by 71
Protein quality control in the nucleolus safeguards recovery of epigenetic regulators after heat shock
Azkanaz, M., López, A. R., de Boer, B., Huiting, W., Angrand, P., Vellenga, E., Kampinga, H. H., Bergink, S., Martens, J. H. A., Schuringa, J. J., et al. (2019) · eLife · doi:10.7554/elife.45205 · Cited by 72
Sequestration of essential proteins causes prion associated toxicity in yeast
Vishveshwara, N., Bradley, M. E., & Liebman, S. W. (2009) · Molecular Microbiology · doi:10.1111/j.1365-2958.2009.06836.x · Cited by 68
Autophagy inhibition promotes defective neosynthesized proteins storage in ALIS, and induces redirection toward proteasome processing and MHCI-restricted presentation
Wenger, T., Terawaki, S., Camosseto, V., Rassoul, R. A., Mies, A., Catalan, N., Cláudio, N., Clavarino, G., Gassart, A. D., Rigotti, F., et al. (2012) · Autophagy · doi:10.4161/auto.18806 · Cited by 72
Normal levels of the antiprion proteins Btn2 and Cur1 cure most newly formed [URE3] prion variants
Wickner, R. B., Bezsonov, E. E., & Bateman, D. A. (2014) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1409582111 · Cited by 68
Asymmetric Inheritance of Aggregated Proteins and Age Reset in Yeast Are Regulated by Vac17-Dependent Vacuolar Functions
Hill, S. M., Hao, X., Grönvall, J., Spikings-Nordby, S., Widlund, P. O., Amen, T., Jörhov, A., Josefson, R., Kaganovich, D., Liu, B., et al. (2016) · Cell Reports · doi:10.1016/j.celrep.2016.06.016 · Cited by 70
Self-citation
Protein aggregation as a mechanism of adaptive cellular responses
Saarikangas, J., & Barral, Y. (2016) · Current Genetics · doi:10.1007/s00294-016-0596-0 · Cited by 67
The mystery of aging and rejuvenation—a budding topic
Nyström, T., & Liu, B. (2014) · Current Opinion in Microbiology · doi:10.1016/j.mib.2014.02.003 · Cited by 71
Chaperone-Mediated Protein Disaggregation Triggers Proteolytic Clearance of Intra-nuclear Protein Inclusions
den Brave, F., Cairo, L. V., Jagadeesan, C., Ruger-Herreros, C., Mogk, A., Bukau, B., & Jentsch, S. (2020) · Cell Reports · doi:10.1016/j.celrep.2020.107680 · Cited by 67
Visualizing the Multistep Process of Protein Aggregation in Live Cells
Ye, S., Hsiung, C., Tang, Y., & Zhang, X. (2022) · Accounts of Chemical Research · doi:10.1021/acs.accounts.1c00648 · Cited by 66
Metabolic engineering for single-cell protein production from renewable feedstocks and its applications
Zhuang, Z., Wan, G., Lu, X., Xie, L., Yu, T., & Tang, H. (2024) · Advanced Biotechnology · doi:10.1007/s44307-024-00042-8 · Cited by 66
Selective destruction of abnormal proteins by ubiquitin-mediated protein quality control degradation
Fredrickson, E. K., & Gardner, R. G. (2012) · Seminars in Cell and Developmental Biology · doi:10.1016/j.semcdb.2011.12.006 · Cited by 66
Chaperones in autophagy
Kaushik, S., & Cuervo, A. M. (2012) · Pharmacological Research · doi:10.1016/j.phrs.2012.10.002 · Cited by 66
Get3 is a holdase chaperone and moves to deposition sites for aggregated proteins when membrane targeting is blocked
Powis, K., Schrul, B., Tienson, H. L., Gostimskaya, I. S., Breker, M., High, S., Schuldiner, M., Jakob, U., & Schwappach, B. (2012) · Journal of Cell Science · doi:10.1242/jcs.112151 · Cited by 67
A yeast model of optineurin proteinopathy reveals a unique aggregation pattern associated with cellular toxicity
Kryndushkin, D. S., Ihrke, G., Piermartiri, T., & Shewmaker, F. P. (2012) · Molecular Microbiology · doi:10.1111/mmi.12075 · Cited by 66
Monitoring the Dynamics of Proteome Aggregation in Live Cells Using a Solubilized and Noncovalent Analogue of Fluorescent Protein Chromophores
Wan, W., Jin, W., Huang, Y., Xia, Q., Bai, Y., Lyu, H., Liu, D., Dong, X., Li, W., & Liu, Y. (2020) · Analytical Chemistry · doi:10.1021/acs.analchem.0c04309 · Cited by 66
Molecular determinants of selective clearance of protein inclusions by autophagy
Wong, E. S. P., Bejarano, E., Rakshit, M., Lee, K., Hanson, H. H., Zaarur, N., Phillips, G. R., Sherman, M. Y., & Cuervo, A. M. (2012) · Nature Communications · doi:10.1038/ncomms2244 · Cited by 68
Role of Posttranslational Protein Modifications in Epididymal Sperm Maturation and Extracellular Quality Control
Cornwall, G. A. (2014) · Advances in experimental medicine and biology · doi:10.1007/978-1-4939-0817-2_8 · Cited by 65
Cellular sequestrases maintain basal Hsp70 capacity ensuring balanced proteostasis
Ho, C.-T., Groušl, T., Shatz, O., Jawed, A., Ruger-Herreros, C., Semmelink, M. F. W., Zahn, R., Richter, K., Bukau, B., & Mogk, A. (2019) · Nature Communications · doi:10.1038/s41467-019-12868-1 · Cited by 67
Aggresomal sequestration and STUB1-mediated ubiquitylation during mammalian proteaphagy of inhibited proteasomes
Choi, W. H., Yun, Y., Park, S., Jeon, J. H., Lee, J., Lee, J. H., Yang, S., Kim, N.-K., Jung, C. H., Kwon, Y. T., et al. (2020) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1920327117 · Cited by 67
The two faces of Janus: functional interactions and protein aggregation
Pastore, A., & Temussi, P. A. (2011) · Current Opinion in Structural Biology · doi:10.1016/j.sbi.2011.11.007 · Cited by 63
Prolonged starvation drives reversible sequestration of lipid biosynthetic enzymes and organelle reorganization inSaccharomyces cerevisiae
Suresh, H. G., dos Santos, A. X. D. S., Kukulski, W., Tyedmers, J., Riezman, H., Bukau, B., & Mogk, A. (2015) · Molecular Biology of the Cell · doi:10.1091/mbc.e14-11-1559 · Cited by 63
AtAIRP2 E3 Ligase Affects ABA and High-Salinity Responses by Stimulating Its ATP1/SDIRIP1 Substrate Turnover
Oh, T. R., Kim, J. H., Cho, S. K., Ryu, M. Y., Yang, S. W., & Kim, W. T. (2017) · PLANT PHYSIOLOGY · doi:10.1104/pp.17.00467 · Cited by 64
Is Lewy pathology in the human nervous system chiefly an indicator of neuronal protection or of toxicity?
Chartier, S., & Duyckaerts, C. J. (2018) · Cell and Tissue Research · doi:10.1007/s00441-018-2854-6 · Cited by 71
Proteasome dynamics
Enenkel, C. (2013) · Biochimica et Biophysica Acta (BBA) - Molecular Cell Research · doi:10.1016/j.bbamcr.2013.03.023 · Cited by 69
Intracellular localization of the proteasome in response to stress conditions
Enenkel, C., Kang, R. W., Wilfling, F., & Ernst, O. P. (2022) · Journal of Biological Chemistry · doi:10.1016/j.jbc.2022.102083 · Cited by 66
Towards a unifying mechanism for ClpB/Hsp104-mediated protein disaggregation and prion propagationThis paper is one of a selection of papers published in this special issue entitled 8th International Conference on AAA Proteins and has undergone the Journal's usual peer review process.
Haslberger, T., Bukau, B., & Mogk, A. (2010) · Biochemistry and Cell Biology · doi:10.1139/o09-118 · Cited by 62
Peroxiredoxin Chaperone Activity Is Critical for Protein Homeostasis in Zinc-deficient Yeast*
MacDiarmid, C. W., Taggart, J., Kerdsomboon, K., Kubisiak, M., Panascharoen, S., Schelble, K., & Eide, D. J. (2013) · Journal of Biological Chemistry · doi:10.1074/jbc.m113.512384 · Cited by 63
Compartmentalization of ER-Bound Chaperone Confines Protein Deposit Formation to the Aging Yeast Cell
Saarikangas, J., Caudron, F., Prasad, R., Moreno, D. F., Bolognesi, A., Aldea, M., & Barral, Y. (2017) · Current Biology · doi:10.1016/j.cub.2017.01.069 · Cited by 62
Subcellular localization of the J-protein Sis1 regulates the heat shock response
Feder, Z. A., Ali, A., Singh, A., Krakowiak, J., Zheng, X., Bindokas, V. P., Wolfgeher, D. J., Kron, S. J., & Pincus, D. (2020) · The Journal of Cell Biology · doi:10.1083/jcb.202005165 · Cited by 61
Physiological and environmental control of yeast prions
Chernova, T. A., Wilkinson, K. D., & Chernoff, Y. O. (2013) · FEMS Microbiology Reviews · doi:10.1111/1574-6976.12053 · Cited by 62
ROR1 is essential for proper innervation of auditory hair cells and hearing in humans and mice
Diaz‐Horta, O., Abad, C., Sennaroğlu, L., Foster, J. M., DeSmidt, A. A., Bademci, G., Tokgöz-Yılmaz, S., Duman, D., Cengiz, F. B., Grati, M., et al. (2016) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1522512113 · Cited by 61
A Fluorogenic AggTag Method Based on Halo‐ and SNAP‐Tags to Simultaneously Detect Aggregation of Two Proteins in Live Cells
Jung, K. H., Kim, S. F., Liu, Y., & Zhang, X. (2019) · ChemBioChem · doi:10.1002/cbic.201800782 · Cited by 62
Chaperoning erythropoiesis
Weiss, M. J., & dos Santos, C. O. (2008) · Blood · doi:10.1182/blood-2008-09-115238 · Cited by 67
Ethanol exposure increases mutation rate through error-prone polymerases
Voordeckers, K., Colding, C., Grasso, L., Pardo, B., Hoes, L., Kominek, J., Gielens, K., Dekoster, K., Gordon, J., van der Zande, E., et al. (2020) · Nature Communications · doi:10.1038/s41467-020-17447-3 · Cited by 60
How the Nucleus Copes with Proteotoxic Stress
Shibata, Y., & Morimoto, R. I. (2014) · Current Biology · doi:10.1016/j.cub.2014.03.033 · Cited by 63
The Hsc/Hsp70 Co-Chaperone Network Controls Antigen Aggregation and Presentation during Maturation of Professional Antigen Presenting Cells
Kettern, N., Rogon, C., Limmer, A., Schild, H., & Höhfeld, J. (2011) · PLoS ONE · doi:10.1371/journal.pone.0016398 · Cited by 60
Exposure of bipartite hydrophobic signal triggers nuclear quality control of Ndc10 at the endoplasmic reticulum/nuclear envelope
Furth, N., Gertman, O., Shiber, A., Alfassy, O. S., Cohen, I., Rosenberg, M. M., Kleinberger-Doron, N., Friedler, A., & Ravid, T. (2011) · Molecular Biology of the Cell · doi:10.1091/mbc.e11-05-0463 · Cited by 60
Get closer and make hotspots: liquid–liquid phase separation in plants
Kim, J., Lee, H., Lee, H. G., & Seo, P. J. (2021) · EMBO Reports · doi:10.15252/embr.202051656 · Cited by 59
The Hsp70/90 cochaperone, Sti1, suppresses proteotoxicity by regulating spatial quality control of amyloid-like proteins
Wolfe, K. J., Ren, H. Y., Trepte, P., & Cyr, D. (2013) · Molecular Biology of the Cell · doi:10.1091/mbc.e13-06-0315 · Cited by 62
Blm10 facilitates nuclear import of proteasome core particles
Weberruss, M. H., Savulescu, A. F., Jando, J., Bissinger, T., Harel, A., Glickman, M. H., & Enenkel, C. (2013) · The EMBO Journal · doi:10.1038/emboj.2013.192 · Cited by 59
Protein Quality Control During Erythropoiesis and Hemoglobin Synthesis
Khandros, E., & Weiss, M. J. (2010) · Hematology/Oncology Clinics of North America · doi:10.1016/j.hoc.2010.08.013 · Cited by 61
Polyprenols Are Synthesized by a Plastidial cis-Prenyltransferase and Influence Photosynthetic Performance
Akhtar, T. A., Surowiecki, P., Siekierska, H., Kania, M., Gelder, K. V., Rea, K. A., Virta, L. K. A., Vatta, M., Gawarecka, K., Wójcik, J., et al. (2017) · The Plant Cell · doi:10.1105/tpc.16.00796 · Cited by 58
Protein aggregation in cell biology: An aggregomics perspective of health and disease
Cox, D., Raeburn, C., Sui, X., & Hatters, D. M. (2018) · Seminars in Cell and Developmental Biology · doi:10.1016/j.semcdb.2018.05.003 · Cited by 60
Disease-Associated Mutant Ubiquitin Causes Proteasomal Impairment and Enhances the Toxicity of Protein Aggregates
Tank, E. M. H., & True, H. L. (2009) · PLoS Genetics · doi:10.1371/journal.pgen.1000382 · Cited by 58
Nuclear and cytoplasmic spatial protein quality control is coordinated by nuclear–vacuolar junctions and perinuclear ESCRT
Sontag, E. M., Morales-Polanco, F., Chen, J.-H., McDermott, G., Dolan, P., Gestaut, D. R., Gros, M. A. L., Larabell, C. A., & Frydman, J. (2023) · Nature Cell Biology · doi:10.1038/s41556-023-01128-6 · Cited by 60
Self-citation
Regulation of Chaperone Effects on a Yeast Prion by Cochaperone Sgt2
Kiktev, D. A., Patterson, J. C., Müller, S., Bariar, B., Pan, T., & Chernoff, Y. O. (2012) · Molecular and Cellular Biology · doi:10.1128/mcb.00875-12 · Cited by 57
RuvbL1 and RuvbL2 enhance aggresome formation and disaggregate amyloid fibrils
Zaarur, N., Xu, X., Lestienne, P. P., Meriin, A. B., McComb, M. E., Costello, C. E., Newnam, G. P., Ganti, R., Romanova, N. V., Shanmugasundaram, M., et al. (2015) · The EMBO Journal · doi:10.15252/embj.201591245 · Cited by 59
Ligand-switchable Substrates for a Ubiquitin-Proteasome System
Egeler, E. L., Urner, L. M., Rakhit, R., Liu, C. W., & Wandless, T. J. (2011) · Journal of Biological Chemistry · doi:10.1074/jbc.m111.264101 · Cited by 56
Routing Misfolded Proteins through the Multivesicular Body (MVB) Pathway Protects against Proteotoxicity
Wang, S., Thibault, G., & Ng, D. (2011) · Journal of Biological Chemistry · doi:10.1074/jbc.m111.233346 · Cited by 57
HSPB8 and BAG3 cooperate to promote spatial sequestration of ubiquitinated proteins and coordinate the cellular adaptive response to proteasome insufficiency
Guilbert, S. M., Lambert, H., Rodrigue, M., Fuchs, M., Landry, J., & Lavoie, J. N. (2018) · The FASEB Journal · doi:10.1096/fj.201700558rr · Cited by 56
Prefoldin Promotes Proteasomal Degradation of Cytosolic Proteins with Missense Mutations by Maintaining Substrate Solubility
Comyn, S. A., Young, B. P., Loewen, C. J. R., & Mayor, T. (2016) · PLoS Genetics · doi:10.1371/journal.pgen.1006184 · Cited by 56
Polyglutamine Toxicity Is Controlled by Prion Composition and Gene Dosage in Yeast
Gong, H., Romanova, N. V., Allen, K., Chandramowlishwaran, P., Gokhale, K., Newnam, G. P., Mieczkowski, P. A., Sherman, M. Y., & Chernoff, Y. O. (2012) · PLoS Genetics · doi:10.1371/journal.pgen.1002634 · Cited by 55
Amyloids and Yeast Prion Biology
Wickner, R. B., Edskes, H. K., Bateman, D. A., Kelly, A. C., Gorkovskiy, A., Dayani, Y., & Zhou, A. E. (2013) · Biochemistry · doi:10.1021/bi301686a · Cited by 55
Organelle segregation during mitosis: Lessons from asymmetrically dividing cells
Ouellet, J., & Barral, Y. (2012) · The Journal of Cell Biology · doi:10.1083/jcb.201102078 · Cited by 55
The Protein Quality Control Machinery Regulates Its Misassembled Proteasome Subunits
Peters, L. Z., Karmon, O., David-Kadoch, G., Hazan, R., Yu, Z., Glickman, M. H., & Ben‐Aroya, S. (2015) · PLoS Genetics · doi:10.1371/journal.pgen.1005178 · Cited by 55
Ubiquitin orchestrates proteasome dynamics between proliferation and quiescence in yeast
Gu, Z. C., Wu, E., Sailer, C., Jando, J., Styles, E. B., Eisenkolb, I., Kuschel, M., Bitschar, K., Wang, X., Huang, L., et al. (2017) · Molecular Biology of the Cell · doi:10.1091/mbc.e17-03-0162 · Cited by 55
There Is an Inclusion for That: Material Properties of Protein Granules Provide a Platform for Building Diverse Cellular Functions
Kaganovich, D. (2017) · Trends in Biochemical Sciences · doi:10.1016/j.tibs.2017.08.002 · Cited by 57
Self-citation
The basic machineries for mitochondrial protein quality control
Vazquez‐Calvo, C., Suhm, T., Büttner, S., & Ott, M. (2019) · Mitochondrion · doi:10.1016/j.mito.2019.10.003 · Cited by 56
Intracellular Dynamics of the Ubiquitin-Proteasome-System
Chowdhury, M., & Enenkel, C. (2015) · F1000Research · doi:10.12688/f1000research.6835.1 · Cited by 58
An Evolutionary Trade-Off between Protein Turnover Rate and Protein Aggregation Favors a Higher Aggregation Propensity in Fast Degrading Proteins
Baets, G. D., Reumers, J., Delgado, J., Dopazo, J., Schymkowitz, J. W. H., & Rousseau, F. (2011) · PLoS Computational Biology · doi:10.1371/journal.pcbi.1002090 · Cited by 54
Opposing roles of Ubp3‐dependent deubiquitination regulate replicative life span and heat resistance
Öling, D., Eisele, F., Kvint, K., & Nyström, T. (2014) · The EMBO Journal · doi:10.1002/embj.201386822 · Cited by 54
Luciferase NanoLuc as a reporter for gene expression and protein levels in Saccharomyces cerevisiae
Masser, A. E., Kandasamy, G., Kaimal, J. M., & Andréasson, C. (2016) · Yeast · doi:10.1002/yea.3155 · Cited by 54
Hsp70–Hsp110 chaperones deliver ubiquitin-dependent and -independent substrates to the 26S proteasome for proteolysis in yeast
Kandasamy, G., & Andréasson, C. (2018) · Journal of Cell Science · doi:10.1242/jcs.210948 · Cited by 54
Protein Kinases Are Associated with Multiple, Distinct Cytoplasmic Granules in Quiescent Yeast Cells
Shah, K. H., Nostramo, R., Zhang, B., Varia, S. N., Klett, B. M., & Herman, P. K. (2014) · Genetics · doi:10.1534/genetics.114.172031 · Cited by 53
Fusion of Protein Aggregates Facilitates Asymmetric Damage Segregation
Coelho, M., Lade, S. J., Alberti, S., Groß, T., & Tolić, I. M. (2014) · PLoS Biology · doi:10.1371/journal.pbio.1001886 · Cited by 56

Authors: Kaganovich, D., Kopito, R., & Frydman, J.
Affiliations: Stanford University (US)
Corresponding author: Frydman, Judith
ORCID: Kaganovich, Daniel
Kopito, Ron
Frydman, Judith
Venue: Nature
Publisher: Springer Science and Business Media LLC
Published: 2008-08
Volume: 454
Issue: 7208
Pages: 1088-1095
ISSN: 0028-0836 (ISSN-L)
1476-4687
DOI: 10.1038/nature07195
PMC: PMC2746971
OpenAlex: W1967025628
Cited by: 932
References: 57
Citations by year: 2026: 24 · 2025: 29 · 2024: 41 · 2023: 47 · 2022: 40 · 2021: 52 · 2020: 55 · 2019: 53 · 2018: 54 · 2017: 76 · 2016: 74 · 2015: 65 · 2014: 71 · 2013: 59 · 2012: 58
FWCI: 18.36
Type: journal article
Language: en
Open access: green
www.ncbi.nlm.nih.gov
Licence: www.springer.com/tdm (tdm)
Locations: Nature (publishedVersion)
PubMed (publishedVersion)
PubMed Central (acceptedVersion)
RePEc: Research Papers in Economics (submittedVersion)
ePrints Soton (University of Southampton) (submittedVersion)
Funders: National Institutes of Health
National Institute of General Medical Sciences (R01GM056433)
National Institute of Neurological Disorders and Stroke (R01NS042842)
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Heat shock proteins research
Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Autophagy in Disease and Therapy
Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Genetic Neurodegenerative Diseases
Keywords: protein misfolding, protein quality control, ubiquitination, proteasome, protein aggregation, huntingtin, prion protein, autophagy, neurodegenerative diseases, yeast, mammalian cells
MeSH terms: Ubiquitin-Conjugating Enzyme UBC9, Cytosol, HeLa Cells, Humans, Prions, Proteins, Saccharomyces cerevisiae, Solubility, Protein Folding, Ubiquitin-Conjugating Enzymes, Proteasome Endopeptidase Complex, Von Hippel-Lindau Tumor Suppressor Protein, Ubiquitination

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

Misfolded proteins partition between two distinct quality control compartments

Abstract

Overview

Integrity signals

Verification

Claims the paper makes

Claims other papers make about this one

Self-check

Citations

Cites

Cited by

Related

Metadata

Record

About these checks