The DOI matches its Crossref record; 56 of the 56 references it cites were found in a registry or an index.
SUMOylation at K340 inhibits tau degradation through deregulating its phosphorylation and ubiquitination
Open accessAbstract
Significance: Intracellular accumulation of the abnormally modified tau is hallmark pathology of AD, but the mechanism leading to tau aggregation is not fully characterized. In the present study, we studied the effects of tau SUMOylation on its phosphorylation, ubiquitination, degradation, and aggregation. We discovered that sumoylation competes with ubiquitination in modifying tau, correlating with tau hyperphosphorylation. Identification of the posttranslational modification on tau provides the new insight into the molecular mechanism in tau aggregation.
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“Tau sumoylation may be pathogenic, as SUMO1 immunoreactivity was found to correlate with phosphorylated tau in AD patient brain.”
From Molecular and cellular mechanisms underlying the pathogenesis of Alzheimer’s disease (2020) · cites this paper as [173]
In the citing paper
“Sumoylation enhances tau phosphorylation, but reduces tau ubiquitination and UPS-mediated degradation [173].”
From Molecular and cellular mechanisms underlying the pathogenesis of Alzheimer’s disease (2020) · cites this paper as [173]
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Cites
1 retracted
Buschmann, T., Fuchs, S. Y., Lee, C.-G., Pan, Z., & Ronai, Z. A. (2000) · Cell · doi:10.1016/s0092-8674(00)80887-9 · Cited by 267
RetractedThe Ubiquitin-Proteasome Proteolytic Pathway: Destruction for the Sake of Construction
Glickman, M. H., & Ciechanover, A. J. (2002) · Physiological Reviews · doi:10.1152/physrev.00027.2001 · Cited by 4,296
Grundke-Iqbal, I., Iqbal, K., Tung, Y. C., Quinlan, M., Wisniewski, H. M., & Binder, L. I. (1986) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.83.13.4913 · Cited by 3,676
Lee, V. M.-Y., Goedert, M., & Trojanowski, J. Q. (2001) · Annual Review of Neuroscience · doi:10.1146/annurev.neuro.24.1.1121 · Cited by 2,480
Hay, R. T. (2005) · Molecular Cell · doi:10.1016/j.molcel.2005.03.012 · Cited by 1,656
Extensive Involvement of Autophagy in Alzheimer Disease: An Immuno-Electron Microscopy Study
Nixon, R. A., Wegiel, J., Kumar, A., Yu, W. H., Peterhoff, C., Cataldo, A., & Cuervo, A. M. (2005) · Journal of Neuropathology & Experimental Neurology · doi:10.1093/jnen/64.2.113 · Cited by 1,588
SUMO-1 Modification of IκBα Inhibits NF-κB Activation
Desterro, J. M. P., Rodríguez, M. S., & Hay, R. T. (1998) · Molecular Cell · doi:10.1016/s1097-2765(00)80133-1 · Cited by 1,050
Alonso, A. D. C., Grundke-Iqbal, I., & Iqbal, K. (1996) · Nature Medicine · doi:10.1038/nm0796-783 · Cited by 859
Ubiquitin Is a Component of Paired Helical Filaments in Alzheimer's Disease
Mori, H., Kondo, J., & Ihara, Y. (1987) · Science · doi:10.1126/science.3029875 · Cited by 843
Köpke, E., Tung, Y. C., Shaikh, S., Alonso, A. C., Iqbal, K., & Grundke-Iqbal, I. (1993) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(20)80536-5 · Cited by 779
Alzheimer's Disease: A Central Role for Amyloid
Selkoe, D. J. (1994) · Journal of Neuropathology & Experimental Neurology · doi:10.1097/00005072-199409000-00003 · Cited by 752
Role of abnormally phosphorylated tau in the breakdown of microtubules in Alzheimer disease.
Alonso, A. C., Zaidi, T., Grundke-Iqbal, I., & Iqbal, K. (1994) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.91.12.5562 · Cited by 738
DEFECTIVE BRAIN MICROTUBULE ASSEMBLY IN ALZHEIMER'S DISEASE
Iqbal, K., Zaidi, T., Wen, G. Y., Grundke, I., MERZ, P. A., Shaikh, S., Wisniewski, H., Alafuzoff, I. I., & Winblad, B. G. (1986) · The Lancet · doi:10.1016/s0140-6736(86)92134-3 · Cited by 737
The acetylation of tau inhibits its function and promotes pathological tau aggregation
Cohen, T. J., Guo, J. L., Hurtado, D. E., Kwong, L. K., Mills, I. P., Trojanowski, J. Q., & Lee, V. M. Y. (2011) · Nature Communications · doi:10.1038/ncomms1255 · Cited by 724
CHIP and Hsp70 regulate tau ubiquitination, degradation and aggregation
Petrucelli, L. (2004) · Human Molecular Genetics · doi:10.1093/hmg/ddh083 · Cited by 723 · cited 1×
“When the cells are exposed to the stresses, CHIP, a ubiquitin ligase that interacts directly with Hsp70/90, can induce tau ubiquitination and thus selectively reduce the level of detergent insoluble tau (17).”
BackgroundPost-translational modifications of tau protein: Implications for Alzheimer's disease
Martin, L., Latypova, X., & Terro, F. (2011) · Neurochemistry International · doi:10.1016/j.neuint.2010.12.023 · Cited by 683
Gong, C., & Iqbal, K. (2008) · Current Medicinal Chemistry · doi:10.2174/092986708785909111 · Cited by 673
Perry, G., Friedman, R., Shaw, G., & Chau, V (1987) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.84.9.3033 · Cited by 623
β-Amyloid protein increases the vulnerability of cultured cortical neurons to excitotoxic damage
Koh, J., Yang, L. L., & Cotman, C. W. (1990) · Brain Research · doi:10.1016/0006-8993(90)91355-k · Cited by 617
Kinases and phosphatases and tau sites involved in Alzheimer neurofibrillary degeneration
Wang, J., Grundke, I., & Iqbal, K. (2007) · European Journal of Neuroscience · doi:10.1111/j.1460-9568.2006.05226.x · Cited by 569
Self-citationMicrotubule-associated protein tau in development, degeneration and protection of neurons
Wang, J., & Liu, F. (2008) · Progress in Neurobiology · doi:10.1016/j.pneurobio.2008.03.002 · Cited by 405
Self-citationGong, C.-X., Lidsky, T., Wegiel, J., Zuck, L., Grundke-Iqbal, I., & Iqbal, K. (2000) · Journal of Biological Chemistry · doi:10.1074/jbc.275.8.5535 · Cited by 405
GSK-3 is essential in the pathogenesis of Alzheimer's disease
Takashima, A. (2006) · Journal of Alzheimer s Disease · doi:10.3233/jad-2006-9s335 · Cited by 403
Ginkgolic Acid Inhibits Protein SUMOylation by Blocking Formation of the E1-SUMO Intermediate
Fukuda, I., Ito, A., Hirai, G., Nishimura, S., Kawasaki, H., Saitoh, H., Kimura, K.-I., Sodeoka, M., & Yoshida, M. (2009) · Chemistry & Biology · doi:10.1016/j.chembiol.2009.01.009 · Cited by 355
Granular Tau Oligomers as Intermediates of Tau Filaments
Maeda, S., Sahara, N., Saito, Y., Murayama, M., Yoshiike, Y., Kim, H., Miyasaka, T., Murayama, S., Ikai, A., & Takashima, A. (2007) · Biochemistry · doi:10.1021/bi061359o · Cited by 330
Ubiquitin and its kin: how close are the family ties?
Jentsch, S., & Pyrowolakis, G. (2000) · Trends in Cell Biology · doi:10.1016/s0962-8924(00)01785-2 · Cited by 322
The Endosomal-Lysosomal System of Neurons in Alzheimer's Disease Pathogenesis: A Review
Nixon, R. A., Cataldo, A. M., & Mathews, P. M. (2000) · Neurochemical Research · doi:10.1023/a:1007675508413 · Cited by 320
Small Ubiquitin-like Modifier (SUMO) Modification of Natively Unfolded Proteins Tau and α-Synuclein
Dorval, V., & Fraser, P. E. (2006) · Journal of Biological Chemistry · doi:10.1074/jbc.m510127200 · Cited by 319
Hershko, A., Eytan, E., Ciechanover, A. J., & Haas, A. L. (1982) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(19)45327-1 · Cited by 290
Microtubule-Associated Protein Tau
Yen, S.-H. C., Nacharaju, P., Ko, L., Kenessey, Á., & Liu, W.-K. (1998) · Elsevier eBooks · doi:10.1016/b978-012734610-6/50012-9 · Cited by 284
Hamano, T., Gendron, T. F., Causevic, E., Yen, S., Lin, W., Isidoro, C., DeTure, M., & Ko, L. (2008) · European Journal of Neuroscience · doi:10.1111/j.1460-9568.2008.06084.x · Cited by 283
Dohmen, R. J. (2004) · Biochimica et Biophysica Acta (BBA) - Molecular Cell Research · doi:10.1016/j.bbamcr.2004.09.021 · Cited by 273
Small Ubiquitin-like Modifier (SUMO) Recognition of a SUMO Binding Motif
Song, J., Zhang, Z., Hu, W., & Chen, Y. (2005) · Journal of Biological Chemistry · doi:10.1074/jbc.m507059200 · Cited by 264
Alzheimer neurofibrillary degeneration: significance, etiopathogenesis, therapeutics and prevention
Iqbal, K., & Grundke, I. (2008) · Journal of Cellular and Molecular Medicine · doi:10.1111/j.1582-4934.2008.00225.x · Cited by 243
Zhu, L.-Q., Wang, S.-H., Liu, D., Yin, Y.-Y., Tian, Q., Wang, X.-C., Wang, Q., Chen, J.-G., & Wang, J.-Z. (2007) · The Journal of Neuroscience · doi:10.1523/jneurosci.3321-07.2007 · Cited by 234
Self-citationMutual interactions between the SUMO and ubiquitin systems: a plea of no contest
Ulrich, H. D. (2005) · Trends in Cell Biology · doi:10.1016/j.tcb.2005.08.002 · Cited by 198
SUMO on the road to neurodegeneration
Dorval, V., & Fraser, P. E. (2007) · Biochimica et Biophysica Acta (BBA) - Molecular Cell Research · doi:10.1016/j.bbamcr.2007.03.017 · Cited by 188
A Caspase Cleaved Form of Tau Is Preferentially Degraded through the Autophagy Pathway
Dolan, P. J., & Johnson, G. V. W. (2010) · Journal of Biological Chemistry · doi:10.1074/jbc.m110.110940 · Cited by 147
GSK-3β Is Required for Memory Reconsolidation in Adult Brain
Kimura, T., Yamashita, S., Nakao, S., Park, J.-M., Murayama, M., Mizoroki, T., Yoshiike, Y., Sahara, N., & Takashima, A. (2008) · PLoS ONE · doi:10.1371/journal.pone.0003540 · Cited by 138
Tau Phosphorylation, Tangles, and Neurodegeneration
Geschwind, D. H. (2003) · Neuron · doi:10.1016/s0896-6273(03)00681-0 · Cited by 129
Microtubule-associated polypeptides tau are altered in Alzheimer paired helical filaments
Grundke, I., VORBRODT, A. W., Iqbal, K., Tung, Y. C., Wang, G. P., & Wisniewski, H. M. (1988) · Molecular Brain Research · doi:10.1016/0169-328x(88)90017-4 · Cited by 128
Phosphoprotein Phosphatase 2A: A Novel Druggable Target for Alzheimer’s Disease
Voronkov, M. V., Braithwaite, S. P., & Stock, J. B. (2011) · Future Medicinal Chemistry · doi:10.4155/fmc.11.47 · Cited by 127
Cytosolic Proteolysis of τ by Cathepsin D in Hippocampus Following Suppression of Cathepsins B and L
Bednarski, E., & LYNCH, G. S. (1996) · Journal of Neurochemistry · doi:10.1046/j.1471-4159.1996.67051846.x · Cited by 110
Ubiquitination and abnormal phosphorylation of paired helical filaments in Alzheimer's disease
Iqbal, K., & Grundke, I. (1991) · Molecular Neurobiology · doi:10.1007/bf02935561 · Cited by 108
SUMO-1 marks the nuclear inclusions in familial neuronal intranuclear inclusion disease
Pountney, D. L., Huang, Y. M., Burns, R. J., Haan, E., Thompson, P. D., Blumbergs, P. C., & Gai, W. P. (2003) · Experimental Neurology · doi:10.1016/j.expneurol.2003.07.004 · Cited by 107
Alzheimer neurofibrillary tangles: Monoclonal antibodies to inherent antigen(s)
Wang, G. P., Grundke, I., Kascsak, R., Iqbal, K., & Wisniewski, H. M. (1984) · Acta Neuropathologica · doi:10.1007/bf00687608 · Cited by 103
Aggregation of Detergent-insoluble Tau Is Involved in Neuronal Loss but Not in Synaptic Loss
Kimura, T., Fukuda, T., Sahara, N., Yamashita, S., Murayama, M., Mizoroki, T., Yoshiike, Y., Lee, B., Sotiropoulos, I., Maeda, S., et al. (2010) · Journal of Biological Chemistry · doi:10.1074/jbc.m110.136630 · Cited by 97
Grune, T., Botzen, D., Engels, M., Voß, P., Kaiser, B., Jung, T., Grimm, S., Ermak, G., & Davies, K. J. A. (2010) · Archives of Biochemistry and Biophysics · doi:10.1016/j.abb.2010.05.008 · Cited by 85
Iqbal, K., Alonso, A. D. C., & Grundke, I. (2008) · Journal of Alzheimer s Disease · doi:10.3233/jad-2008-14402 · Cited by 77
Takahashi, K., Ishida, M., Komano, H., & Takahashi, H. (2008) · Neuroscience Letters · doi:10.1016/j.neulet.2008.06.012 · Cited by 75
Potential Compensatory Responses Through Autophagic/Lysosomal Pathways in Neurodegenerative Diseases
Butler, D., Nixon, R. A., & Bahr, B. A. (2006) · Autophagy · doi:10.4161/auto.2729 · Cited by 56
Peng, J.-H., Zhang, C.-E., Wei, W., Hong, X., Pan, X., & Wang, J. (2007) · Neuropharmacology · doi:10.1016/j.neuropharm.2007.02.008 · Cited by 41
Self-citationGenetic Evidence That Polysumoylation Bypasses the Need for a SUMO-Targeted Ub Ligase
Mullen, J. R., Das, M. M., & Brill, S. J. (2010) · Genetics · doi:10.1534/genetics.110.124347 · Cited by 31
Lee, E. J., Hyun, S. H., Chun, J., Shin, S. H., Yeon, K. H., Kwak, M. K., Park, T. Y., & Kang, S. S. (2008) · The Open Biochemistry Journal · doi:10.2174/1874091x00802010067 · Cited by 26
Neuronal death and GSK-3β: a tau fetish?
Mattson, M. P. (2001) · Trends in Neurosciences · doi:10.1016/s0166-2236(00)01838-5 · Cited by 22
Fighting Bax: towards a Parkinson's disease therapy
Ploix, C. C., & Spier, A. D. (2001) · Trends in Neurosciences · doi:10.1016/s0166-2236(00)01837-3 · Cited by 5
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Self-citationRoles of tau protein in health and disease
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Metadata
- Authors
- Luo, H.-B., Xia, Y.-Y., Shu, X.-J., Liu, Z.-C., Feng, Y., Liu, X.-H., Yu, G., Yin, G., Xiong, Y.-S., Zeng, K., Jiang, J., Ye, K., Wang, X.-C., & Wang, J.-Z.
- Affiliations
- Department of Pathophysiology, School of Basic Medicine, Key Laboratory of Ministry of Education of China for Neurological Disorders, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China;
- Department of Pathology and Pathophysiology, School of Medicine, Jianghan University, Wuhan 430056, China;
- Huazhong University of Science and Technology (CN)
- Emory University (US)
- Nantong University (CN)
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2014-11-05
- Volume
- 111
- Issue
- 46
- Pages
- 16586-16591
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC4246270
- OpenAlex
- W1996406602
- Cited by
- 236
- References
- 56
- Citations by year
- 2026: 18 · 2025: 22 · 2024: 23 · 2023: 23 · 2022: 21 · 2021: 30 · 2020: 19 · 2019: 15 · 2018: 22 · 2017: 20 · 2016: 13 · 2015: 10
- FWCI
- 9.56
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Natural Science Foundation of China (NSFC) (81271405)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Alzheimer's disease research and treatments
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Ubiquitin and proteasome pathways
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Keywords
- tau hyperphosphorylation, tau degradation, Alzheimer's disease, SUMO1, ginkgolic acid, amyloid-beta, tau aggregation, hippocampal neurons, cerebral cortex
- MeSH terms
- Glycogen Synthase Kinase 3 beta, Wortmannin, Alzheimer Disease, Androstadienes, Animals, Cerebral Cortex, Female, Hippocampus, Humans, Indoles, Male, Maleimides, Middle Aged, Nerve Tissue Proteins, Peptide Fragments, Phosphorylation, Protein Processing, Post-Translational, Recombinant Fusion Proteins, Salicylates, Solubility, Amyloid beta-Peptides, Mutagenesis, Site-Directed, tau Proteins, Rats, Sprague-Dawley, Point Mutation, Amino Acid Substitution, Mutation, Missense, SUMO-1 Protein, Glycogen Synthase Kinase 3, Proteasome Endopeptidase Complex, Rats, Ubiquitination, HEK293 Cells, Sumoylation, Proteolysis
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