Cited by 723Alzheimer's disease research and treatmentsHeat shock proteins researchUbiquitin and proteasome pathways

The DOI matches its Crossref record; 42 of the 42 references it cites were found in a registry or an index.

CHIP and Hsp70 regulate tau ubiquitination, degradation and aggregation

Petrucelli, L.·2004·Human Molecular Genetics

Open this paper in CoChat — free account

Abstract

Molecular chaperones, ubiquitin ligases and proteasome impairment have been implicated in several neurodegenerative diseases, including Alzheimer's and Parkinson's disease, which are characterized by accumulation of abnormal protein aggregates (e.g. tau and alpha-synuclein respectively). Here we report that CHIP, an ubiquitin ligase that interacts directly with Hsp70/90, induces ubiquitination of the microtubule associated protein, tau. CHIP also increases tau aggregation. Consistent with this observation, diverse of tau lesions in human postmortem tissue were found to be immunopositive for CHIP. Conversely, induction of Hsp70 through treatment with either geldanamycin or heat shock factor 1 leads to a decrease in tau steady-state levels and a selective reduction in detergent insoluble tau. Furthermore, 30-month-old mice overexpressing inducible Hsp70 show a significant reduction in tau levels. Together these data demonstrate that the Hsp70/CHIP chaperone system plays an important role in the regulation of tau turnover and the selective elimination of abnormal tau species. Hsp70/CHIP may therefore play an important role in the pathogenesis of tauopathies and also represents a potential therapeutic target.

Integrity signals

Registry

Crossref · 10.1093/hmg/ddh083

Cites

42 of 42 references verified0 citation errors · 0 not checkable

Statistics

Recomputing p-values needs the paper’s full text.

Claims the paper makes

This paper’s full text isn’t openly available, so its claims and self-check weren’t run. The registry and citation checks still apply.

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?

Mutations in the parkin gene cause autosomal recessive juvenile parkinsonism
Kitada, T., Asakawa, S., Hattori, N., Matsumine, H., Yamamura, Y., Minoshima, S., Yokochi, M., Mizuno, Y., & Shimizu, N. (1998) · Nature · doi:10.1038/33416 · Cited by 5,227
Association of missense and 5′-splice-site mutations in tau with the inherited dementia FTDP-17
Hutton, M., Lendon, C. L., Rizzu, P., Baker, M., Froelich, S., Houlden, H., Pickering-Brown, S., Chakraverty, S., Isaacs, A., Grover, A., et al. (1998) · Nature · doi:10.1038/31508 · Cited by 3,498
Multiple isoforms of human microtubule-associated protein tau: sequences and localization in neurofibrillary tangles of Alzheimer's disease
Goedert, M., Spillantini, M. G., Jakes, R., Rutherford, D., & Crowther, R. A. (1989) · Neuron · doi:10.1016/0896-6273(89)90210-9 · Cited by 2,492
Mutation in the tau gene in familial multiple system tauopathy with presenile dementia
Spillantini, M. G., Murrell, J. R., Goedert, M., Farlow, M. R., Klug, A., & Ghetti, B. (1998) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.95.13.7737 · Cited by 1,474
Inhibition of heat shock protein HSP90-pp60v-src heteroprotein complex formation by benzoquinone ansamycins: essential role for stress proteins in oncogenic transformation.
Whitesell, L., Mimnaugh, E. G., De Costa, B., Myers, C. E., & Neckers, L. M. (1994) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.91.18.8324 · Cited by 1,444
Tau is a candidate gene for chromosome 17 frontotemporal dementia
Poorkaj, P., Bird, T. D., Wijsman, E., Nemens, E., Garruto, R. M., Anderson, L., Andreadis, A., Wiederholt, W. C., Raskind, M., & Schellenberg, G. D. (1998) · Annals of Neurology · doi:10.1002/ana.410430617 · Cited by 1,374
Neurofibrillary tangles, amyotrophy and progressive motor disturbance in mice expressing mutant (P301L) tau protein
Lewis, J., McGowan, E., Rockwood, J., Melrose, H., Nacharaju, P., Van Slegtenhorst, M., Gwinn-Hardy, K., Murphy, M. P., Baker, M., Yu, X., et al. (2000) · Nature Genetics · doi:10.1038/78078 · Cited by 1,371
Repression of Heat Shock Transcription Factor HSF1 Activation by HSP90 (HSP90 Complex) that Forms a Stress-Sensitive Complex with HSF1
Zou, J., Guo, Y., Guettouche, T., Smith, D. F., & Voellmy, R. W. (1998) · Cell · doi:10.1016/s0092-8674(00)81588-3 · Cited by 1,232
Chaperone Suppression of α-Synuclein Toxicity in a Drosophila Model for Parkinson's Disease
Auluck, P. K., Chan, H. Y. E., Trojanowski, J. Q., Lee, V. M.-Y., & Bonini, N. M. (2002) · Science · doi:10.1126/science.1067389 · Cited by 1,227
Cloning and sequencing of the cDNA encoding a core protein of the paired helical filament of Alzheimer disease: identification as the microtubule-associated protein tau
Goedert, M., Wischik, C. M., Crowther, R. A., Walker, J. E., & Klug, A. (1988) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.85.11.4051 · Cited by 1,134

Flagged first, then by citations

Show all 41 references

Sorted by citations

Items 101–200 of 719

The Ubiquitin-Proteasome System in Neurodegeneration
McKinnon, C., & Tabrizi, S. J. (2014) · Antioxidants and Redox Signaling · doi:10.1089/ars.2013.5802 · Cited by 175
“In cooperation with Hsc70, CHIP facilitates ubiquitin-dependent degradation of abnormal forms of tau, including hyperphosphorylated tau (56, 151, 167).”
Protein aggregation in the pathogenesis of familial and sporadic Parkinson's disease
McNaught, K. S. P., & Olanow, C. W. (2005) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2005.08.012 · Cited by 166
Revisiting the grammar of Tau aggregation and pathology formation: how new insights from brain pathology are shaping how we study and target Tauopathies
Limorenko, G., & Lashuel, H. A. (2021) · Chemical Society Reviews · doi:10.1039/d1cs00127b · Cited by 168
HSP induction mediates selective clearance of tau phosphorylated at proline-directed Ser/Thr sites but not KXGS (MARK) sites
Dickey, C. A., Dunmore, J., Lu, B., Wang, J., Lee, W. C., Kamal, A., Burrows, F., Eckman, C., Hutton, M., & Petrucelli, L. (2006) · The FASEB Journal · doi:10.1096/fj.05-5343fje · Cited by 160
Self-citation
CHIP Overexpression Reduces Mutant Androgen Receptor Protein and Ameliorates Phenotypes of the Spinal and Bulbar Muscular Atrophy Transgenic Mouse Model
Adachi, H., Waza, M., Tokui, K., Katsuno, M., Minamiyama, M., Tanaka, F., Doyu, M., & Sobue, G. (2007) · Journal of Neuroscience · doi:10.1523/jneurosci.1242-07.2007 · Cited by 157
Hsp70 Structure, Function, Regulation and Influence on Yeast Prions
Sharma, D., & Masison, D. C. (2009) · Protein and Peptide Letters · doi:10.2174/092986609788490230 · Cited by 156
Resveratrol Induces Brain Resilience Against Alzheimer Neurodegeneration Through Proteostasis Enhancement
Corpas, R., Griñán‐Ferré, C., Rodrı́guez-Farré, E., Pallàs, M., & Sanfeliu, C. (2018) · Molecular Neurobiology · doi:10.1007/s12035-018-1157-y · Cited by 164
Reduction of Nuak1 Decreases Tau and Reverses Phenotypes in a Tauopathy Mouse Model
Lasagna‐Reeves, C. A., de Haro, M., Hao, S., Park, J., Rousseaux, M. W. C., Al‐Ramahi, I., Jafar‐Nejad, P., Vilanova-Velez, L., See, L., Maio, A. D., et al. (2016) · Neuron · doi:10.1016/j.neuron.2016.09.022 · Cited by 154
Ataxia and hypogonadism caused by the loss of ubiquitin ligase activity of the U box protein CHIP
Shi, C.-H., Schisler, J. C., Rubel, C. E., Tan, S., Song, B., McDonough, H., Xu, L., Portbury, A. L., Mao, C., True, C. A., et al. (2013) · Human Molecular Genetics · doi:10.1093/hmg/ddt497 · Cited by 158
Protein quality control in Alzheimer's disease by the ubiquitin proteasome system
de Vrij, F. M. S., Fischer, D. F., VANLEEUWEN, F., & Hol, E. M. (2004) · Progress in Neurobiology · doi:10.1016/j.pneurobio.2004.10.001 · Cited by 155
Emerging role of p62/sequestosome-1 in the pathogenesis of Alzheimer's disease
Salminen, A., Kaarniranta, K., Haapasalo, A., Hiltunen, M., Soininen, H., & Alafuzoff, I. (2012) · Progress in Neurobiology · doi:10.1016/j.pneurobio.2011.11.005 · Cited by 153
Molecular pathways that influence human tau-induced pathology in Caenorhabditis elegans
Kraemer, B. C., Burgess, J. K., Chen, J. H., Thomas, J. H., & Schellenberg, G. D. (2006) · Human Molecular Genetics · doi:10.1093/hmg/ddl067 · Cited by 150
“Others showed that tau is one such protein that is ubiquitinated by the CHIP/HSC70 complex mechanism (38,39,70).”
Background
Lysine methylation is an endogenous post-translational modification of tau protein in human brain and a modulator of aggregation propensity
Funk, K. E., Thomas, S. N., Schafer, K. N., Cooper, G. L., Liao, Z., Clark, D. J., Yang, A. J., & Kuret, J. (2014) · Biochemical Journal · doi:10.1042/bj20140372 · Cited by 142
The Chaperone-assisted E3 Ligase C Terminus of Hsc70-interacting Protein (CHIP) Targets PTEN for Proteasomal Degradation
Ahmed, S. F., Deb, S., Paul, I., Chatterjee, A., Mandal, T., Chatterjee, U., & Ghosh, M. K. (2012) · Journal of Biological Chemistry · doi:10.1074/jbc.m111.321083 · Cited by 152
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
CHIP and HSPs interact with β-APP in a proteasome-dependent manner and influence Aβ metabolism
Kumar, P., Ambasta, R. K., Veereshwarayya, V., Rosen, K. M., Kosik, K. S., Band, H., Mestril, R., Patterson, C., & Querfurth, H. W. (2007) · Human Molecular Genetics · doi:10.1093/hmg/ddm030 · Cited by 145
Chaperone Functions of the E3 Ubiquitin Ligase CHIP
Rosser, M. F. N., Washburn, E. K., Muchowski, P. J., Patterson, C., & Cyr, D. (2007) · Journal of Biological Chemistry · doi:10.1074/jbc.m700513200 · Cited by 144
Tau-Based Treatment Strategies in Neurodegenerative Diseases
Schneider, A., & Mandelkow�, E. (2008) · Neurotherapeutics · doi:10.1016/j.nurt.2008.05.006 · Cited by 145
An acetylation–phosphorylation switch that regulates tau aggregation propensity and function
Carlomagno, Y., Chung, D.-E. C., Yue, M., Castanedes-Casey, M., Madden, B. J., Dunmore, J., Tong, J., DeTure, M., Dickson, D. W., Petrucelli, L., et al. (2017) · Journal of Biological Chemistry · doi:10.1074/jbc.m117.794602 · Cited by 143
Self-citation
Differential ubiquitination and degradation of huntingtin fragments modulated by ubiquitin-protein ligase E3A
Bhat, K. P., Yan, S., Wang, C.-E., Li, S., & Li, X. (2014) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1402215111 · Cited by 142
The role of tau phosphorylation and cleavage in neuronal cell death
Chun, W. (2006) · Frontiers in bioscience · doi:10.2741/2097 · Cited by 144
X-linked ubiquitin-specific peptidase 11 increases tauopathy vulnerability in women
Yan, Y., Wang, X., Chaput, D., Shin, M.-K., Koh, Y., Gan, L., Pieper, A. A., Woo, J.-A. A., & Kang, D. E. (2022) · Cell · doi:10.1016/j.cell.2022.09.002 · Cited by 144
Glial Cells as Players in Parkinsonism: The “Good,” the “Bad,” and the “Mysterious” Glia
Mena, M. A., & de Yébenes, J. G. (2008) · The Neuroscientist · doi:10.1177/1073858408322839 · Cited by 141
Chaperone signalling complexes in Alzheimer's disease
Koren, J., Jinwal, U. K., Lee, D. C., Jones, J. R., Shults, C. L., Johnson, A. G., Anderson, L. J., & Dickey, C. A. (2008) · Journal of Cellular and Molecular Medicine · doi:10.1111/j.1582-4934.2008.00557.x · Cited by 141
Lysine-Directed Post-translational Modifications of Tau Protein in Alzheimer's Disease and Related Tauopathies
Kontaxi, C., Piccardo, P., & Gill, A. C. (2017) · Frontiers in Molecular Biosciences · doi:10.3389/fmolb.2017.00056 · Cited by 138
“…ubiquitylate tau, including the C-terminus of the Hsc70-interacting protein (CHIP), TNF receptor-associated factor 6 (TRAF6) and axotrophin/MARCH7 (Petrucelli et al., 2004; Babu et al., 2005; Flach et al., 2014), whereas other E3 ubiquitin ligases, such as parkin and Cbl, failed to ubiquitylate…”
BackgroundInfluential
Natural Cannabinoids Improve Dopamine Neurotransmission and Tau and Amyloid Pathology in a Mouse Model of Tauopathy
Casarejos, M. J., Perucho, J., Gómez, A., Muñoz, M. P., Fernandez-Estévez, M., Sagredo, O., Fernández‐Ruíz, J., Guzmán, M., de Yébenes, J. G., & Mena, M. A. (2013) · Journal of Alzheimer s Disease · doi:10.3233/jad-130050 · Cited by 139
Examining the mechanisms that link β-amyloid and α-synuclein pathologies
Marsh, S. E., & Blurton-Jones, M. M. (2012) · Alzheimer s Research & Therapy · doi:10.1186/alzrt109 · Cited by 140
Ubiquitin pathways in neurodegenerative disease
Atkin, G., & Paulson, H. L. (2014) · Frontiers in Molecular Neuroscience · doi:10.3389/fnmol.2014.00063 · Cited by 140
The Ubiquitin Ligase CHIP Integrates Proteostasis and Aging by Regulation of Insulin Receptor Turnover
Tawo, R., Pokrzywa, W., Kevei, É., Akyuz, M. E., Balaji, V., Adrian, S., Höhfeld, J., & Hoppe, T. (2017) · Cell · doi:10.1016/j.cell.2017.04.003 · Cited by 132
MARKing tau for tangles and toxicity
Drewes, G. (2004) · Trends in Biochemical Sciences · doi:10.1016/j.tibs.2004.08.001 · Cited by 137
Therapeutic strategies for tau mediated neurodegeneration
Yoshiyama, Y., Lee, V. M. ‐., & Trojanowski, J. Q. (2012) · Journal of Neurology Neurosurgery & Psychiatry · doi:10.1136/jnnp-2012-303144 · Cited by 137
Salt Stress–Induced Disassembly of Arabidopsis Cortical Microtubule Arrays Involves 26S Proteasome–Dependent Degradation of SPIRAL1
Wang, S., Kurepa, J., Hashimoto, T., & Smalle, J. (2011) · The Plant Cell · doi:10.1105/tpc.111.089920 · Cited by 131
Tauopathy: A common mechanism for neurodegeneration and brain aging
Saha, P., & Sen, N. (2019) · Mechanisms of Ageing and Development · doi:10.1016/j.mad.2019.01.007 · Cited by 134
Down-regulation of WW Domain-containing Oxidoreductase Induces Tau Phosphorylation in Vitro
Sze, C.-I., Su, M., Pugazhenthi, S., Jambal, P., Hsu, L.-J., Heath, J., Schultz, L., & Chang, N.-S. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.m401399200 · Cited by 130
Hsp90 regulates tau pathology through co-chaperone complexes in Alzheimer's disease
Salminen, A., Ojala, J. O., Kaarniranta, K., Hiltunen, M., & Soininen, H. S. (2010) · Progress in Neurobiology · doi:10.1016/j.pneurobio.2010.10.006 · Cited by 131
“Prion‐Like” Templated Misfolding in Tauopathies
Clavaguera, F., Lavenir, I., Falcon, B., Frank, S., Goedert, M., & Tolnay, M. (2013) · Brain Pathology · doi:10.1111/bpa.12044 · Cited by 133
Tau‐targeted treatment strategies in Alzheimer's disease
Götz, J., Ittner, A., & Ittner, L. M. (2011) · British Journal of Pharmacology · doi:10.1111/j.1476-5381.2011.01713.x · Cited by 130
Heat Shock Protein 70 Prevents both Tau Aggregation and the Inhibitory Effects of Preexisting Tau Aggregates on Fast Axonal Transport
Patterson, K. R., Ward, S. M., Combs, B., Voss, K., Kanaan, N. M., Morfini, G. A., Brady, S. T., Gamblin, T. C., & Binder, L. I. (2011) · Biochemistry · doi:10.1021/bi2009147 · Cited by 128
Loss of HDAC6, a novel CHIP substrate, alleviates abnormal tau accumulation
Cook, C. N., Gendron, T. F., Scheffel, K., Carlomagno, Y., Dunmore, J. H., Deture, M. A., & Petrucelli, L. (2012) · Human Molecular Genetics · doi:10.1093/hmg/dds125 · Cited by 132
Self-citation
Pharmacological Targeting of the Hsp70 Chaperone
Patury, S., Miyata, Y., & Gestwicki, J. E. (2009) · Current Topics in Medicinal Chemistry · doi:10.2174/156802609789895674 · Cited by 130
NMNAT2:HSP90 Complex Mediates Proteostasis in Proteinopathies
Ali, Y., Allen, H. M., Yu, L., Li‐Kroeger, D., Bakhshizadehmahmoudi, D., Hatcher, A., Aubin, C., Xu, J., Bjorklund, N. L., Taglialatela, G., et al. (2016) · PLoS Biology · doi:10.1371/journal.pbio.1002472 · Cited by 131
Hsp70 Inhibits the Nucleation and Elongation of Tau and Sequesters Tau Aggregates with High Affinity
Kundel, F., De, S., Flagmeier, P., Horrocks, M. H., Kjærgaard, M., Shammas, S. L., Jackson, S., Dobson, C. M., & Klenerman, D. (2018) · ACS Chemical Biology · doi:10.1021/acschembio.7b01039 · Cited by 128
Development and Therapeutic Implications of Selective Histone Deacetylase 6 Inhibitors
Kalin, J. H., & Bergman, J. A. (2013) · Journal of Medicinal Chemistry · doi:10.1021/jm4001659 · Cited by 131
Dual modification of Alzheimer’s disease PHF-tau protein by lysine methylation and ubiquitylation: a mass spectrometry approach
Thomas, S. N., Funk, K. E., Wan, Y., Liao, Z., Davies, P., Kuret, J., & Yang, A. J. (2012) · Acta Neuropathologica · doi:10.1007/s00401-011-0893-0 · Cited by 123
“For example, ubiquitylation of tau at Lys residues modulates intracellular tau levels [53, 61], the magnitude of which affects both nucleation and extension phases of the aggregation reaction [12].”
Background
Blocking Aβ 42 Accumulation Delays the Onset and Progression of Tau Pathology via the C Terminus of Heat Shock Protein70-Interacting Protein: A Mechanistic Link between Aβ and Tau Pathology
Oddo, S., Caccamo, A., Tseng, B., Cheng, D., Vasilevko, V., Cribbs, D. H., & LaFerla, F. M. (2008) · Journal of Neuroscience · doi:10.1523/jneurosci.2464-08.2008 · Cited by 125
Phosphorylated tau and the neurodegenerative foldopathies
Kosik, K. S., & Shimura, H. (2004) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2004.10.011 · Cited by 124
SIRT1 Overexpression in Mouse Hippocampus Induces Cognitive Enhancement Through Proteostatic and Neurotrophic Mechanisms
Corpas, R., Revilla, S., Ursulet, S., Castro, M., Kaliman, P., Petegnief, V., Giménez‐Llort, L., Sarkis, C., Pallàs, M., & Sanfeliu, C. (2016) · Molecular Neurobiology · doi:10.1007/s12035-016-0087-9 · Cited by 124
Developing therapeutic approaches to tau, selected kinases, and related neuronal protein targets
Lee, V. M.-Y., Brunden, K. R., Hutton, M., & Trojanowski, J. Q. (2011) · Cold Spring Harbor Perspectives in Medicine · doi:10.1101/cshperspect.a006437 · Cited by 122
Alzheimer's Disease Mechanisms and Emerging Roads to Novel Therapeutics
Sala Frigerio, C., & De Strooper, B. (2016) · Annual Review of Neuroscience · doi:10.1146/annurev-neuro-070815-014015 · Cited by 116
“…tau’s microtubule-binding domains and promotes its degradation through ubiquitination mediated by CHIP (carboxyl terminus of the Hsc70-interacting protein) (Petrucelli et al. 2004), whereas inhibition of Hsp90 reduces the levels of tau phosphorylated at AD-relevant epitopes (Dickey et al. 2006).”
Molecular Chaperone Dysfunction in Neurodegenerative Diseases and Effects of Curcumin
Maiti, P., Manna, J., Veleri, S., & Frautschy, S. A. (2014) · BioMed Research International · doi:10.1155/2014/495091 · Cited by 121
Chronic lithium treatment decreases tau lesions by promoting ubiquitination in a mouse model of tauopathies
Nakashima, H., Ishihara, T., Suguimoto, S. P., Yokota, O., Oshima, E., Kugo, A., Terada, S., Hamamura, T., Trojanowski, J. Q., Lee, V. M. ‐., et al. (2005) · Acta Neuropathologica · doi:10.1007/s00401-005-1087-4 · Cited by 119
Tau interactome mapping based identification of Otub1 as Tau deubiquitinase involved in accumulation of pathological Tau forms in vitro and in vivo
Wang, P., Joberty, G., Buist, A., Vanoosthuyse, A., Stancu, I., Vasconcelos, B., Pierrot, N., Faelth-Savitski, M., Kienlen‐Campard, P., Octave, J., et al. (2017) · Acta Neuropathologica · doi:10.1007/s00401-016-1663-9 · Cited by 120
Disease modifying therapy for AD?1
Golde, T. E. (2006) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.2006.04211.x · Cited by 117
“HSP 90 also promote tau association with microtubules and reduce phospho-tau levels (Petrucelli et al. 2004).”
Background
Targeting Hsp90 and its co-chaperones to treat Alzheimer’s disease
Blair, L. J., Sabbagh, J. J., & Dickey, C. A. (2014) · Expert Opinion on Therapeutic Targets · doi:10.1517/14728222.2014.943185 · Cited by 122
Imbalance of Hsp70 family variants fosters tau accumulation
Jinwal, U. K., Akoury, E., Abisambra, J. F., O’Leary, J. C., Thompson, A. D., Blair, L. J., Jin, Y., Bacon, J. A., Nordhues, B. A., Cockman, M. E., et al. (2012) · The FASEB Journal · doi:10.1096/fj.12-220889 · Cited by 121
Glial Dysfunction in Parkin Null Mice: Effects of Aging
Solano, R. M., Casarejos, M. J., Menéndez-Cuervo, J., Rodríguez‐Navarro, J. A., de Yébenes, J. G., & Mena, M. A. (2008) · Journal of Neuroscience · doi:10.1523/jneurosci.4609-07.2008 · Cited by 119
Barcoding heat shock proteins to human diseases: looking beyond the heat shock response
Kakkar, V., Meister-Broekema, M., Minoia, M., Carra, S., & Kampinga, H. H. (2014) · Disease Models & Mechanisms · doi:10.1242/dmm.014563 · Cited by 116
Pin1 has opposite effects on wild-type and P301L tau stability and tauopathy
Lim, J., Balaštík, M., Lee, T. H., Nakamura, K., Liou, Y., Sun, A., Finn, G., Pastorino, L., Lee, V. M. ‐., & Lu, K. P. (2008) · Journal of Clinical Investigation · doi:10.1172/jci34308 · Cited by 117
Tau Protein Squired by Molecular Chaperones During Alzheimer’s Disease
Gorantla, N. V., & Chinnathambi, S. (2018) · Journal of Molecular Neuroscience · doi:10.1007/s12031-018-1174-3 · Cited by 113
The proteasome as a druggable target with multiple therapeutic potentialities: Cutting and non-cutting edges
Tundo, G. R., Sbardella, D., Santoro, A. M., Coletta, A., Oddone, F., Grasso, G., Milardi, D., Lacal, P. M., Marini, S., Purrello, R., et al. (2020) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2020.107579 · Cited by 120
Autophagy and Tau Protein
Hamano, T., Enomoto, S., Shirafuji, N., Ikawa, M., Yamamura, O., Yen, S.-H. C., & Nakamoto, Y. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22147475 · Cited by 122
Ubiquitin ligase Hrd1 enhances the degradation and suppresses the toxicity of polyglutamine-expanded huntingtin
Yang, H., Zhong, X., Ballar, P., Luo, S., Shen, Y., Rubinsztein, D. C., Monteiro, M. J., & Fang, S. (2006) · Experimental Cell Research · doi:10.1016/j.yexcr.2006.10.031 · Cited by 116
Functional genomic screen and network analysis reveal novel modifiers of tauopathy dissociated from tau phosphorylation
Ambegaokar, S. S., & Jackson, G. R. (2011) · Human Molecular Genetics · doi:10.1093/hmg/ddr432 · Cited by 113
“Tau clearance may involve several processes, as it has been reported that tau can be targeted to lysosomes or cathepsin-mediated degradation (14,15), can be ubiquitinated and targeted to the proteasome (16,17) or can be digested by proteases such as puromycin-sensitive aminopeptidase (PSA) (18,19).”
Background
BAG-1 Associates with Hsc70·Tau Complex and Regulates the Proteasomal Degradation of Tau Protein
Elliott, E., Tsvetkov, P., & Ginzburg, I. (2007) · Journal of Biological Chemistry · doi:10.1074/jbc.m706379200 · Cited by 116
Therapeutic strategies for the treatment of tauopathies: Hopes and challenges
Khanna, M. R., Kovalevich, J., Lee, V. M. ‐., Trojanowski, J. Q., & Brunden, K. R. (2016) · Alzheimer s & Dementia · doi:10.1016/j.jalz.2016.06.006 · Cited by 116
Involvement of calpain in the neuropathogenesis of Alzheimer’s disease
Mahaman, Y. A. R., Huang, F., Afewerky, H. K., Salissou, M. T. M., Bishwajit, G., & Wang, X. (2018) · Medicinal Research Reviews · doi:10.1002/med.21534 · Cited by 110
Cytoskeleton proteins are modulators of mutant tau-induced neurodegeneration in Drosophila
Blard, O., Feuillette, S., Bou, J., Chaumette, B., Frébourg, T., Campion, D., & Lecourtois, M. (2007) · Human Molecular Genetics · doi:10.1093/hmg/ddm011 · Cited by 110
Pharmacogenomics in Alzheimer's Disease
Cacabelos, R. (2008) · Methods in molecular biology · doi:10.1007/978-1-59745-205-2_10 · Cited by 109
Reconsider Alzheimer's disease by the ‘calpain–cathepsin hypothesis’—A perspective review
Yamashima, T. (2013) · Progress in Neurobiology · doi:10.1016/j.pneurobio.2013.02.004 · Cited by 109
It Is All about (U)biquitin: Role of Altered Ubiquitin‐Proteasome System and UCHL1 in Alzheimer Disease
Tramutola, A., Domenico, F. D., Barone, E., Marzia Perluigi, A., & Butterfield, D. A. (2016) · Oxidative Medicine and Cellular Longevity · doi:10.1155/2016/2756068 · Cited by 109
Protein Homeostasis, Aging and Alzheimer’s Disease
Morawe, T., Hiebel, C., Kern, A., & Behl, C. (2012) · Molecular Neurobiology · doi:10.1007/s12035-012-8246-0 · Cited by 105
Amyloid, tau, pathogen infection and antimicrobial protection in Alzheimer’s disease –conformist, nonconformist, and realistic prospects for AD pathogenesis
Li, H., Liu, C.-C., Zheng, H., & Huang, T. Y. (2018) · Translational Neurodegeneration · doi:10.1186/s40035-018-0139-3 · Cited by 103
“Additional posttranslational modifications such as truncation [176–179], ubiquitylation [180, 181],”
Background
Molecular chaperones and neuronal proteostasis
Smith, H., Li, W., & Cheetham, M. E. (2015) · Seminars in Cell and Developmental Biology · doi:10.1016/j.semcdb.2015.03.003 · Cited by 108
The Chemical Biology of Molecular Chaperones—Implications for Modulation of Proteostasis
Brandvold, K. R., & Morimoto, R. I. (2015) · Journal of Molecular Biology · doi:10.1016/j.jmb.2015.05.010 · Cited by 105
Molecular Chaperones as Rational Drug Targets for Parkinsons Disease Therapeutics
Kalia, S. K., Kalia, L. V., & McLean, P. J. (2010) · CNS & Neurological Disorders - Drug Targets · doi:10.2174/187152710793237386 · Cited by 103
The ubiquitin codes in cellular stress responses
Sheng, X., Xia, Z., Yang, H., & Hu, R. (2023) · Protein & Cell · doi:10.1093/procel/pwad045 · Cited by 117
Lithium treatment arrests the development of neurofibrillary tangles in mutant tau transgenic mice with advanced neurofibrillary pathology.
Leroy, K., Ando, K., Héraud, C., Yilmaz, Z., Authelet, M., Boeynaems, J.-M., Buée, L., De Decker, R., & Brion, J.-P. (2010) · Journal of Alzheimer's Disease · doi:10.3233/jad-2010-1276 · Cited by 103
NMNAT suppresses Tau-induced neurodegeneration by promoting clearance of hyperphosphorylated Tau oligomers in a Drosophila model of tauopathy
Ali, Y., Ruan, K., & Zhai, R. G. (2011) · Human Molecular Genetics · doi:10.1093/hmg/ddr449 · Cited by 105
Pathological Changes of Tau Related to Alzheimer’s Disease
Chu, D., & Liu, F. (2018) · ACS Chemical Neuroscience · doi:10.1021/acschemneuro.8b00457 · Cited by 106
Parkin mediates the degradation‐independent ubiquitination of Hsp70
Moore, D. J., West, A. B., Dikeman, D. A., Dawson, V. L., & Dawson, T. M. (2008) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.2008.05261.x · Cited by 101
Open-gate mutants of the mammalian proteasome show enhanced ubiquitin-conjugate degradation
Choi, W. H., de Poot, S. A. H., Lee, J. H., Kim, J. H., Han, D. H., Kim, Y. K., Finley, D. J., & Lee, M. J. (2016) · Nature Communications · doi:10.1038/ncomms10963 · Cited by 100
The Proteasome and Oxidative Stress in Alzheimer's Disease
Bonet-Costa, V., Pomatto, L. C.-D., & Davies, K. J. A. (2016) · Antioxidants & Redox Signaling · doi:10.1089/ars.2016.6802 · Cited by 99
“CHIP has been identified as a chaperon-like E3 ligase, due to its interaction not only with Hsc70 but also with Hsp70 and Hsp90, both of which are critical in protein folding (125).”
Heat Shock Protein 70 in Alzheimer’s Disease
Lu, R.-C., Tan, M., Wang, H., Xie, A., Yu, J., & Tan, L. (2014) · BioMed Research International · doi:10.1155/2014/435203 · Cited by 103
It May Take Inflammation, Phosphorylation and Ubiquitination to ‘Tangle’ in Alzheimer’s Disease
Arnaud, L. T., Robakis, N. K. R. K., & Figueiredo‐Pereira, M. E. (2006) · Neurodegenerative Diseases · doi:10.1159/000095638 · Cited by 104
Brain CHIP: removing the culprits in neurodegenerative disease
Dickey, C. A., Patterson, C., Dickson, D. W., & Petrucelli, L. (2006) · Trends in Molecular Medicine · doi:10.1016/j.molmed.2006.11.003 · Cited by 102
Self-citation
The Ubiquitin Ligase E6-AP Is Induced and Recruited to Aggresomes in Response to Proteasome Inhibition and May Be Involved in the Ubiquitination of Hsp70-bound Misfolded Proteins
Mishra, A., Godavarthi, S. K., Maheshwari, M., Goswami, A., & Jana, N. R. (2009) · Journal of Biological Chemistry · doi:10.1074/jbc.m806804200 · Cited by 99
Modulation of Hsp90 function in neurodegenerative disorders: a molecular-targeted therapy against disease-causing protein
Waza, M., Adachi, H., Katsuno, M., Minamiyama, M., Tanaka, F., Doyu, M., & Sobue, G. (2006) · Journal of Molecular Medicine · doi:10.1007/s00109-006-0066-0 · Cited by 100
Death-associated protein kinase 1 has a critical role in aberrant tau protein regulation and function
Kim, B. M., You, M.-H., Chen, C.-H., Lee, S., Hong, Y., Hong, Y., Kimchi, A., Zhou, X. Z., & Lee, T. H. (2014) · Cell Death & Disease · doi:10.1038/cddis.2014.216 · Cited by 98
CHIP: A Co-chaperone for Degradation by the Proteasome
Edkins, A. L. (2014) · Sub-cellular biochemistry/Subcellular biochemistry · doi:10.1007/978-3-319-11731-7_11 · Cited by 96
Protein aggregation and ER stress
Ogen‐Shtern, N., David, T. B., & Lederkremer, G. Z. (2016) · Brain Research · doi:10.1016/j.brainres.2016.03.044 · Cited by 98
Aggregation of Disordered Proteins Associated with Neurodegeneration
Tsoi, P. S., Quan, M. D., Ferreon, J. C., & Ferreon, A. C. M. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms24043380 · Cited by 103
Identification of Novel Genes That Modify Phenotypes Induced by Alzheimer's β-Amyloid Overexpression in Drosophila
Cao, W., Song, H., Gangi, T., Kelkar, A., Antani, I., Garza, D., & Konsolaki, M. (2008) · Genetics · doi:10.1534/genetics.107.078394 · Cited by 100
Hsc70 Rapidly Engages Tau after Microtubule Destabilization
Jinwal, U. K., O’Leary, J. C., Borysov, S. I., Jones, J. R., Li, Q., Koren, J., Abisambra, J. F., Vestal, G. D., Lawson, L. Y., Johnson, A. G., et al. (2010) · Journal of Biological Chemistry · doi:10.1074/jbc.m110.113753 · Cited by 101
A farnesyltransferase inhibitor activates lysosomes and reduces tau pathology in mice with tauopathy
Hernández, I., Luna, G., Rauch, J. N., Reis, S. A., Giroux, M., Karch, C. M. M., Boctor, D., Sibih, Y., Storm, N. J., Díaz, A., et al. (2019) · Science Translational Medicine · doi:10.1126/scitranslmed.aat3005 · Cited by 95
Chaperones in Neurodegeneration
Lindberg, I., Shorter, J., Wiseman, R. L., Chiti, F., Dickey, C. A., & McLean, P. J. (2015) · Journal of Neuroscience · doi:10.1523/jneurosci.2600-15.2015 · Cited by 97
E6-AP Promotes Misfolded Polyglutamine Proteins for Proteasomal Degradation and Suppresses Polyglutamine Protein Aggregation and Toxicity
Mishra, A., Dikshit, P., Purkayastha, S., Sharma, J., Nukina, N., & Jana, N. R. (2008) · Journal of Biological Chemistry · doi:10.1074/jbc.m706620200 · Cited by 94
LRRK2: a common pathway for parkinsonism, pathogenesis and prevention?
Taylor, J. P., Mata, I. F., & Farrer, M. J. (2006) · Trends in Molecular Medicine · doi:10.1016/j.molmed.2005.12.004 · Cited by 94
Small molecule therapeutics for tauopathy in Alzheimer’s disease: Walking on the path of most resistance
Wang, L., Bharti, Kumar, R., Pavlov, P. F., & Winblad, B. (2021) · European Journal of Medicinal Chemistry · doi:10.1016/j.ejmech.2020.112915 · Cited by 92
The Role of HSP70 and Its Co-chaperones in Protein Misfolding, Aggregation and Disease
Duncan, E. J., Cheetham, M. E., Chapple, J. P., & van der Spuy, J. (2014) · Sub-cellular biochemistry/Subcellular biochemistry · doi:10.1007/978-3-319-11731-7_12 · Cited by 96
The toxicity of tau in Alzheimer disease: turnover, targets and potential therapeutics
Pritchard, S. M., Dolan, P. J., Vitkus, A., & Johnson, G. V. W. (2011) · Journal of Cellular and Molecular Medicine · doi:10.1111/j.1582-4934.2011.01273.x · Cited by 89
“However, another report [87] asserted the opposite: recognition of tau by CHIP occurred independent of its phosphorylation.”
Background

Authors: Petrucelli, L.
Affiliations: Mayo Clinic in Florida (US)
Corresponding author: Petrucelli, L.
ORCID: Petrucelli, L.
Venue: Human Molecular Genetics
Publisher: Oxford University Press (OUP)
Published: 2004-01-28
Volume: 13
Issue: 7
Pages: 703-714
ISSN: 0964-6906 (ISSN-L)
1460-2083
DOI: 10.1093/hmg/ddh083
OpenAlex: W2168079270
Cited by: 723
References: 41
Citations by year: 2026: 29 · 2025: 36 · 2024: 32 · 2023: 32 · 2022: 37 · 2021: 37 · 2020: 36 · 2019: 25 · 2018: 35 · 2017: 31 · 2016: 31 · 2015: 38 · 2014: 34 · 2013: 28 · 2012: 31
FWCI: 10.76
Type: journal article
Language: en
Open access: closed
Locations: Human Molecular Genetics (publishedVersion)
PubMed (publishedVersion)
UCL Discovery (University College London) (submittedVersion)
Funders: National Institute of Neurological Disorders and Stroke (R01NS041816, R01-NS41816-01)
Topics: Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Alzheimer's disease research and treatments
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Heat shock proteins research
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Ubiquitin and proteasome pathways
Keywords: CHIP, HSP70, tau protein, ubiquitination, protein degradation, tau aggregation, molecular chaperones, ubiquitin ligase, geldanamycin, heat shock factor 1, tauopathy, Alzheimer's disease, Parkinson's disease, proteasome
MeSH terms: Heat Shock Transcription Factors, Animals, Cell Line, Detergents, DNA-Binding Proteins, Genetic Vectors, Humans, Immunohistochemistry, Lac Operon, Models, Genetic, Mutation, Nuclear Proteins, Protein Binding, Quinones, Subcellular Fractions, Transcription Factors, Transfection, Blotting, Western, Benzoquinones, tau Proteins, Molecular Chaperones, HSP70 Heat-Shock Proteins, Transgenes, COS Cells, Ubiquitin, Drosophila Proteins, Ubiquitin-Protein Ligases, Cell Line, Tumor, Lactams, Macrocyclic, Immunoprecipitation, Mice

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

CHIP and Hsp70 regulate tau ubiquitination, degradation and aggregation

Abstract

Overview

Integrity signals

Verification

Claims the paper makes

Claims other papers make about this one

Citations

Cites

Cited by

Related

Metadata

Record

About these checks