A novel mechanism for the regulation of amyloid precursor protein metabolism
Open accessAbstract
Modifier of cell adhesion protein (MOCA; previously called presenilin [PS] binding protein) is a DOCK180-related molecule, which interacts with PS1 and PS2, is localized to brain areas involved in Alzheimer's disease (AD) pathology, and is lost from the soluble fraction of sporadic Alzheimer's disease (AD) brains. Because PS1 has been associated with γ-secretase activity, MOCA may be involved in the regulation of β-amyloid precursor protein (APP) processing. Here we show that the expression of MOCA decreases both APP and amyloid β-peptide secretion and lowers the rate of cell-substratum adhesion. In contrast, MOCA does not lower the secretion of amyloid precursor-like protein (APLP) or several additional type 1 membrane proteins. The phenotypic changes caused by MOCA are due to an acceleration in the rate of intracellular APP degradation. The effect of MOCA expression on the secretion of APP and cellular adhesion is reversed by proteasome inhibitors, suggesting that MOCA directs nascent APP to proteasomes for destruction. It is concluded that MOCA plays a major role in APP metabolism and that the effect of MOCA on APP secretion and cell adhesion is a downstream consequence of MOCA-directed APP catabolism. This is a new mechanism by which the expression of APP is regulated.
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In vitro experiments have shown that induced expression of DOCK3 results in attenuated Aβ secretion through regulation of APP degradation.
“In vitro experiments have shown that induced expression of DOCK3 results in attenuated Aβ secretion through regulation of APP degradation (80, 81).”
From RHO to the DOCK for GDP disembarking: Structural insights into the DOCK GTPase nucleotide exchange factors (2021) · cites this paper as [80]
The Results section ('MOCA reduces APP and Aβ secretion'; page not provided) reports that MOCA-expressing B103 cells secreted considerably less Aβ. The Discussion (page not provided) attributes the reduction to accelerated intracellular APP degradation. Our copy calls the expressed protein MOCA but does not establish that it is DOCK3, so the claim’s identification of the protein is not verified by this source alone. (LLM, conf=0.80)
Experimental — accuracy not yet measuredThere is already evidence that DOCK4 could be involved with AD and DBP.
“There is already evidence that DOCK4 could be involved with AD and DBP.”
From Multi-trait association studies discover pleiotropic loci between Alzheimer’s disease and cardiometabolic traits (2021) · cites this paper as [49]
The Introduction and Results discuss MOCA and its relationship to DOCK180, not DOCK4. The passages retrieved for “DOCK4 DBP” and “DOCK4 involvement Alzheimer disease bipolar disorder” provide no evidence about DOCK4 or DBP, so this copy does not establish the claimed involvement. (LLM, conf=0.76)
Experimental — accuracy not yet measuredPrevious genetic studies have shown that DOCK4 variants are associated with multiple neurological phenotypes.
“Previous genetic studies have shown that DOCK4 variants are associated with multiple neurological phenotypes, and DOCK2, the other member of DOCK4’s protein subfamily, expression is increased in the microglia of patient’s with AD [49, 50].”
From Multi-trait association studies discover pleiotropic loci between Alzheimer’s disease and cardiometabolic traits (2021) · cites this paper as [49]
The Introduction discusses MOCA, its similarity to DOCK180, and presenilin mutations linked to familial Alzheimer’s disease; it does not report genetic studies of DOCK4 variants. Searches for DOCK4 variants and neurological phenotypes found no passage addressing the claimed association in our copy. (LLM, conf=0.76)
Experimental — accuracy not yet measuredDOCK2 expression is increased in the microglia of patients with AD.
“Previous genetic studies have shown that DOCK4 variants are associated with multiple neurological phenotypes, and DOCK2, the other member of DOCK4’s protein subfamily, expression is increased in the microglia of patient’s with AD [49, 50].”
From Multi-trait association studies discover pleiotropic loci between Alzheimer’s disease and cardiometabolic traits (2021) · cites this paper as [49]
The Introduction and Results discuss MOCA and DOCK180, while the Abstract describes MOCA in Alzheimer’s disease. Searches for DOCK2 expression and microglia in patients with Alzheimer’s disease found no passage addressing the claimed increase. (LLM, conf=0.76)
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Cites
Cloning of a gene bearing missense mutations in early-onset familial Alzheimer's disease
Sherrington, R., Rogaev, E. I., Liang, Y., Rogaeva, E. A., Levesque, G., Ikeda, M., Chi, H., Lin, C., Li, G., Holman, K., et al. (1995) · Nature · doi:10.1038/375754a0 · Cited by 4,051 · see citing works
Scheuner, D., Eckman, C., Jensen, M., Song, X., Citron, M., Suzuki, N., Bird, T. D., Hardy, J., Hutton, M., Kukull, W., et al. (1996) · Nature Medicine · doi:10.1038/nm0896-864 · Cited by 2,599 · see citing works
A presenilin-1-dependent γ-secretase-like protease mediates release of Notch intracellular domain
De Strooper, B., Annaert, W., Cupers, P., Saftig, P., Craessaerts, K., Mumm, J. S., Schroeter, E. H., Schrijvers, V., Wolfe, M. S., Ray, W. J., et al. (1999) · Nature · doi:10.1038/19083 · Cited by 2,100 · see citing works
Rogaev, E. I., Sherrington, R., Rogaeva, E. A., Levesque, G., Ikeda, M., Liang, Y., Chi, H., Lin, C., Holman, K., Tsuda, T., et al. (1995) · Nature · doi:10.1038/376775a0 · Cited by 2,052 · see citing works
Amyloid β-peptide is produced by cultured cells during normal metabolism
Haass, C., Schlossmacher, M. G., Hung, A. Y., Vigo-Pelfrey, C., Mellon, A., Ostaszewski, B. L., Lieberburg, I., Koo, E. H., Schenk, D., Teplow, D. B., et al. (1992) · Nature · doi:10.1038/359322a0 · Cited by 1,921 · see citing works
Rapid degradation of a large fraction of newly synthesized proteins by proteasomes
Schubert, U., Antón, L. C., Gibbs, J. S., Norbury, C. C., Yewdell, J. W., & Bennink, J. R. (2000) · Nature · doi:10.1038/35008096 · Cited by 1,536 · see citing works
Borchelt, D. R., Thinakaran, G., Eckman, C. B., Lee, M. K., Davenport, F., Ratovitsky, T., Prada, C.-M., Kim, G., Seekins, S., Yager, D., et al. (1996) · Neuron · doi:10.1016/s0896-6273(00)80230-5 · Cited by 1,478 · see citing works
Protein Oligomerization In The Endoplasmic Reticulum
Hurtley, S. M., & Helenius, A. (1989) · Annual Review of Cell Biology · doi:10.1146/annurev.cb.05.110189.001425 · Cited by 1,002 · see citing works
Epoxomicin, a potent and selective proteasome inhibitor, exhibits in vivo antiinflammatory activity
Meng, L., Mohan, R., Kwok, B. H. B., Elofsson, M., Sin, N., & Crews, C. M. (1999) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.96.18.10403 · Cited by 926 · see citing works
Presenilin is required for activity and nuclear access of Notch in Drosophila
Struhl, G., & Greenwald, I. (1999) · Nature · doi:10.1038/19091 · Cited by 804 · see citing works
Clonal cell lines from the rat central nervous system
Schubert, D. A., Heinemann, S. F., Carlisle, W., Tarikas, H., Kimes, B. W., Patrick, J. W., Steinbach, J. H., Culp, W., & Brandt, B. L. (1974) · Nature · doi:10.1038/249224a0 · Cited by 713 · see citing works
Self-citationMarambaud, P., Shioi, J., Serban, G., Georgakopoulos, A., Sarner, S., Nagy, V., Baki, L., Wen, P., Efthimiopoulos, S., Shao, Z., et al. (2002) · The EMBO Journal · doi:10.1093/emboj/21.8.1948 · Cited by 686 · see citing works
Protein degradation in the endoplasmic reticulum
Klausner, R. D., & Sitia, R. (1990) · Cell · doi:10.1016/0092-8674(90)90104-m · Cited by 653 · see citing works
Proteolytic processing and cell biological functions of the amyloid precursor protein
Strooper, B. D., & Annaert, W. G. (2000) · Journal of Cell Science · doi:10.1242/jcs.113.11.1857 · Cited by 628 · see citing works
LIN-12/Notch signaling: lessons from worms and fliesPreprint
Greenwald, I. (1998) · Genes & Development · doi:10.1101/gad.12.12.1751 · Cited by 541 · see citing works
Presenilin-1 mutations downregulate the signalling pathway of the unfolded-protein response
Katayama, T., Imaizumi, K., Sato, N., Miyoshi, K., Kudo, T., Hitomi, J., Morihara, T., Yoneda, T., Gomi, F., Mori, Y., et al. (1999) · Nature Cell Biology · doi:10.1038/70265 · Cited by 521 · see citing works
Transition-state analogue inhibitors of γ-secretase bind directly to presenilin-1
Esler, W. P., Kimberly, W. T., Ostaszewski, B. L., Diehl, T. S., Moore, C. L., Tsai, J.-Y., Rahmati, T., Xia, W., Selkoe, D. J., & Wolfe, M. S. (2000) · Nature Cell Biology · doi:10.1038/35017062 · Cited by 514 · see citing works
Neurogenic phenotypes and altered Notch processing in Drosophila Presenilin mutants
Ye, Y., Lukinova, N. I., & Fortini, M. (1999) · Nature · doi:10.1038/19096 · Cited by 492 · see citing works
Cook, D. G., Forman, M. S., Sung, J. C., Leight, S., Kolson, D. L., Iwatsubo, T., Lee, V. M.-Y., & Doms, R. W. (1997) · Nature Medicine · doi:10.1038/nm0997-1021 · Cited by 439 · see citing works
Cellular mechanisms of β-amyloid production and secretion
Sinha, S., & Lieberburg, I. M. (1999) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.96.20.11049 · Cited by 438 · see citing works
Lactacystin, Proteasome Function, and Cell Fate
Fenteany, G., & Schreiber, S. L. (1998) · Journal of Biological Chemistry · doi:10.1074/jbc.273.15.8545 · Cited by 414 · see citing works
Craiu, A., Gaczynska, M. E., Akopian, T. N., Gramm, C. F., Fenteany, G., Goldberg, A. L., & Rock, K. L. (1997) · Journal of Biological Chemistry · doi:10.1074/jbc.272.20.13437 · Cited by 382 · see citing works
Protein Topology of Presenilin 1
Doan, A., Thinakaran, G., Borchelt, D., Slunt, H. H., Ratovitski, T., Podlisny, M. B., Selkoe, D. J., Seeger, M., Gandy, S., Price, D. L., et al. (1996) · Neuron · doi:10.1016/s0896-6273(00)80232-9 · Cited by 371 · see citing works
Effects of PS1 Deficiency on Membrane Protein Trafficking in Neurons
Naruse, S., Thinakaran, G., Luo, J.-J., Kusiak, J. W., Tomita, T., Iwatsubo, T., Qian, X., Ginty, D. D., Price, D. L., Borchelt, D. R., et al. (1998) · Neuron · doi:10.1016/s0896-6273(00)80637-6 · Cited by 355 · see citing works
The regulation of amyloid β protein precursor secretion and its modulatory role in cell adhesion
Schubert, D. A., Jin, L.-W., Saitoh, T., & Cole, G. M. (1989) · Neuron · doi:10.1016/0896-6273(89)90237-7 · Cited by 353 · see citing works
Self-citationWolfe, M. S., Xia, W., Moore, C. L., Leatherwood, D. D., Ostaszewski, B., Rahmati, T., Donkor, I. O., & Selkoe, D. J. (1999) · Biochemistry · doi:10.1021/bi982562p · Cited by 289 · see citing works
Xu, H., Sweeney, D. A., Wang, R., Thinakaran, G., Lo, A., Sisodia, S. S., Greengard, P., & Gandy, S. (1997) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.94.8.3748 · Cited by 281 · see citing works
Niwa, M., Sidrauski, C., Kaufman, R. J., & Walter, P. (1999) · Cell · doi:10.1016/s0092-8674(00)81667-0 · Cited by 276 · see citing works
Alternative splicing generates a secreted form of N-CAM in muscle and brain
Gower, H. J., Barton, C. H., Elsom, V. L., Thompson, J., Moore, S. E., Dickson, G., & Walsh, F. S. (1988) · Cell · doi:10.1016/0092-8674(88)90241-3 · Cited by 241 · see citing works
Regulation of Amyloid Precursor Protein Cleavage
Mills, J., & Reiner, P. B. (1999) · Journal of Neurochemistry · doi:10.1046/j.1471-4159.1999.0720443.x · Cited by 221 · see citing works
A Substrate-Based Difluoro Ketone Selectively Inhibits Alzheimer's γ-Secretase Activity
Wolfe, M. S., Citron, M., Diehl, T. S., Xia, W., Donkor, I. O., & Selkoe, D. J. (1998) · Journal of Medicinal Chemistry · doi:10.1021/jm970621b · Cited by 214 · see citing works
Characterization of a Presenilin-mediated Amyloid Precursor Protein Carboxyl-terminal Fragment γ
Yu, C., Kim, S.-H., Ikeuchi, T., Xu, H., Gasparini, L., Wang, R., & Sisodia, S. S. (2001) · Journal of Biological Chemistry · doi:10.1074/jbc.c100410200 · Cited by 210 · see citing works
Caporaso, G. L., Gandy, S., Buxbaum, J. D., & Greengard, P. (1992) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.89.6.2252 · Cited by 204 · see citing works
Jin, L., Ninomiya, H., Roch, J., Schubert, D. A., Masliah, E., Otero, D. A., & Saitoh, T. (1994) · Journal of Neuroscience · doi:10.1523/jneurosci.14-09-05461.1994 · Cited by 198 · see citing works
Self-citationN-CAM and N-Cadherin Expression during in Vitro Chondrogenesis
Tavella, S., Raffo, P., Tacchetti, C., Cancedda, R., & Castagnola, P. (1994) · Experimental Cell Research · doi:10.1006/excr.1994.1352 · Cited by 188 · see citing works
The Chaperone BiP/GRP78 Binds to Amyloid Precursor Protein and Decreases Aβ40 and Aβ42 Secretion
Yang, Y., Turner, R. S., & Gaut, J. R. (1998) · Journal of Biological Chemistry · doi:10.1074/jbc.273.40.25552 · Cited by 179 · see citing works
Beher, D., Hesse, L., Masters, C. L., & Multhaup, G. (1996) · Journal of Biological Chemistry · doi:10.1074/jbc.271.3.1613 · Cited by 170 · see citing works
Presenilin-1 differentially facilitates endoproteolysis of the β-amyloid precursor protein and Notch
Capell, A., Steiner, H., Romig, H., Keck, S., Baader, M., Grim, M. G., Baumeister, R., & Haass, C. (2000) · Nature Cell Biology · doi:10.1038/35008626 · Cited by 147 · see citing works
Higaki, J. N., Quon, D. H., Zhong, Z., & Cordell, B. (1995) · Neuron · doi:10.1016/0896-6273(95)90322-4 · Cited by 145 · see citing works
Xia, W., Ray, W. J., Ostaszewski, B. L., Rahmati, T., Kimberly, W. T., Wolfe, M. S., Zhang, J., Goate, A., & Selkoe, D. J. (2000) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.97.16.9299 · Cited by 133 · see citing works
The Role of Presenilins in γ-Secretase Activity
Wolfe, M. S., & Haass, C. (2001) · Journal of Biological Chemistry · doi:10.1074/jbc.r000026200 · Cited by 132 · see citing works
Schubert, D. A., & Behl, C. (1993) · Brain Research · doi:10.1016/0006-8993(93)91331-l · Cited by 131 · see citing works
Self-citationParvathy, S., Hussain, I., Karran, E. H., Turner, A. J., & Hooper, N. M. (1998) · Biochemistry · doi:10.1021/bi972034y · Cited by 123 · see citing works
Berezovska, O., Jack, C. E., McLean, P. J., Aster, J. C., Hicks, C. D., Xia, W., Wolfe, M. S., Kimberly, W. T., Weinmaster, G., Selkoe, D. J., et al. (2000) · Journal of Neurochemistry · doi:10.1046/j.1471-4159.2000.0750583.x · Cited by 119 · see citing works
Role of the proteasome in Alzheimer’s disease
Checler, F., da Costa, C. A., Ancolio, K., Chevallier, N., Lopez‐Perez, E., & Marambaud, P. (2000) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/s0925-4439(00)00039-9 · Cited by 98 · see citing works
Galbete, J. L., Martin, T. R., PERESSINI, E., Modena, P., Bianchi, R., & Forloni, G. (2000) · Biochemical Journal · doi:10.1042/bj3480307 · Cited by 97 · see citing works
Chen, M., & Yankner, B. A. (1991) · Neuroscience Letters · doi:10.1016/0304-3940(91)90034-q · Cited by 96 · see citing works
Sherwood, S. W., Kung, A. L., Roitelman, J., Simoni, R., & SCHIMKE, R. T. (1993) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.90.8.3353 · Cited by 91 · see citing works
Soriano, S., Chyung, A. S. C., Chen, X., Stokin, G. B., Lee, V. M. ‐., & Koo, E. H. (1999) · Journal of Biological Chemistry · doi:10.1074/jbc.274.45.32295 · Cited by 89 · see citing works
Xu, X., Yang, D., Wyss‐Coray, T., Yan, J. S., Gan, L., Sun, Y., & Mucke, L. (1999) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.96.13.7547 · Cited by 86 · see citing works
Caporaso, G. (1992) · Medical Entomology and Zoology · Cited by 80 · see citing works
Complex, Two-way Traffic of Molecules Across the Membrane of the Endoplasmic Reticulum
Suzuki, T., Yan, Q., & Lennarz, W. J. (1998) · Journal of Biological Chemistry · doi:10.1074/jbc.273.17.10083 · Cited by 78 · see citing works
Zhang, L., Song, L., & Parker, E. M. (1999) · Journal of Biological Chemistry · doi:10.1074/jbc.274.13.8966 · Cited by 70 · see citing works
Isolation and Characterization of Novel Presenilin Binding Protein
Kashiwa, A., Yoshida, H., Lee, S., Paladino, T., Liu, Y., Chen, Q., Dargusch, R., Schubert, D. A., & Kimura, H. (2000) · Journal of Neurochemistry · doi:10.1046/j.1471-4159.2000.0750109.x · Cited by 69 · see citing works
Self-citationBinding Partners of Alzheimer's Disease Proteins: Are They Physiologically Relevant?
Gassen, G. V., Annaert, W. G., & Broeckhoven, C. V. (2000) · Neurobiology of Disease · doi:10.1006/nbdi.2000.0306 · Cited by 59 · see citing works
Coulson, E. J., Barrett, G. L., Storey, E., Bartlett, P. F., Beyreuther, K. T., & Masters, C. L. (1997) · Brain Research · doi:10.1016/s0006-8993(97)00757-9 · Cited by 52 · see citing works
Figueiredo‐Pereira, M. E., Efthimiopoulos, S., Tezapsidis, N., Buku, A., Ghiso, J. A., Mehta, P. D., & Robakis, N. K. R. K. (1999) · Journal of Neurochemistry · doi:10.1046/j.1471-4159.1999.721417.x · Cited by 46 · see citing works
Proteasome Inhibitors Induce the Association of Alzheimer's Amyloid Precursor Protein with Hsc73
Kouchi, Z., Sorimachi, H., Suzuki, K., & Ishiura, S. (1999) · Biochemical and Biophysical Research Communications · doi:10.1006/bbrc.1998.9977 · Cited by 44 · see citing works
Wu, A., Pangalos, M. N., Efthimiopoulos, S., Shioi, J., & Robakis, N. K. R. K. (1997) · Journal of Neuroscience · doi:10.1523/jneurosci.17-13-04987.1997 · Cited by 43 · see citing works
Bunnell, W. L., Pham, H. V., & Glabe, C. G. (1998) · Journal of Biological Chemistry · doi:10.1074/jbc.273.48.31947 · Cited by 37 · see citing works
Chen, Q., Yoshida, H., Schubert, D., Maher, P. A., Mallory, M. E., & Masliah, E. (2001) · American Journal Of Pathology · doi:10.1016/s0002-9440(10)63005-2 · Cited by 33 · see citing works
Self-citationHeat shock alters Alzheimer's β amyloid precursor protein expression in human endothelial cells
Ciallella, J. R., Rangnekar, V., & McGillis, J. P. (1994) · Journal of Neuroscience Research · doi:10.1002/jnr.490370611 · Cited by 31 · see citing works
Shepherd, C. E., Bowes, S., Parkinson, D., Cambray-Deakin, M. A., & Pearson, R. C. A. (2000) · Neuroscience · doi:10.1016/s0306-4522(00)00197-4 · Cited by 23 · see citing works
An Accomplice for γ-Secretase Brought into Focus
Sisodia, S. S. (2000) · Science · doi:10.1126/science.289.5488.2296 · Cited by 18 · see citing works
Protease Inhibitors Divert Amyloid Precursor Protein to the Secretory Pathway
Hare, J. F. (2001) · Biochemical and Biophysical Research Communications · doi:10.1006/bbrc.2001.4507 · Cited by 9 · see citing works
Presenilin 1 expression in yeast lowers secretion of the amyloid precursor protein
Evin, G. M., Brocque, D. L., Culvenor, J. G., Galatis, D., Weidemann, A., Beyreuther, K. T., Masters, C. L., & Cappai, R. (2000) · Neuroreport · doi:10.1097/00001756-200002070-00036 · Cited by 6 · see citing works
Flagged first, then by citations
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Sorted by citations
Côté, J., & Vuori, K. (2002) · Journal of Cell Science · doi:10.1242/jcs.00219 · Cited by 412 · see citing works
DOCK4, a GTPase activator, is disrupted during tumorigenesis.
Yajnik, V., Paulding, C., Sordella, R., McClatchey, A. I., Saito, M., Wahrer, D. C. R., Reynolds, P., Bell, D. W., Lake, R., van den Heuvel, S., et al. (2003) · Cell · doi:10.1016/s0092-8674(03)00155-7 · Cited by 230 · see citing works
Grimsley, C. M., Kinchen, J. M., Tosello-Trampont, A.-C., Brugnera, E., Haney, L. B., Lu, M., Chen, Q., Klingele, D., Hengartner, M. O., & Ravichandran, K. S. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.m307087200 · Cited by 224 · see citing works
Self-citationKaneko, M., Koike, H., Saito, R., Kitamura, Y., Okuma, Y., & Nomura, Y. (2010) · Journal of Neuroscience · doi:10.1523/jneurosci.2422-09.2010 · Cited by 201 · see citing works
Localization and Processing of the Amyloid-β Protein Precursor in Mitochondria-Associated Membranes
Prete, D. D., Suski, J., Oulès, B., Debayle, D., Gay, A.-S., Lacas-Gervais, S., Bussiere, R., Bauer, C., Pinton, P., Paterlini-Bréchot, P., et al. (2016) · Journal of Alzheimer's Disease · doi:10.3233/jad-160953 · Cited by 158 · see citing works
Presenilin diversifies its portfolio
Parks, A. L., & Curtis, D. (2007) · Trends in Genetics · doi:10.1016/j.tig.2007.01.008 · Cited by 150 · see citing works
Determinants of conformational dimerization of Mad2 and its inhibition by p31comet
Mapelli, M., Filipp, F. V., Rancati, G. I., Massimiliano, L., Nezi, L., Stier, G., Hagan, R. S., Confalonieri, S., Piatti, S., Sattler, M., et al. (2006) · The EMBO Journal · doi:10.1038/sj.emboj.7601033 · Cited by 137 · see citing works
PH domain of ELMO functions in trans to regulate Rac activation via Dock180
Lu, M., Kinchen, J. M., Rossman, K. L., Grimsley‐Myers, C. M., deBakker, C. D., Brugnera, E., Tosello‐Trampont, A., Haney, L. B., Klingele, D., Sondek, J., et al. (2004) · Nature Structural & Molecular Biology · doi:10.1038/nsmb800 · Cited by 130 · see citing works
BubR1 acetylation at prometaphase is required for modulating APC/C activity and timing of mitosis
Choi, E., Choe, H., Min, J., Choi, J. Y., Kim, J., & Lee, H. (2009) · The EMBO Journal · doi:10.1038/emboj.2009.123 · Cited by 126 · see citing works
Ruusala, A., & Aspenström, P. (2004) · FEBS Letters · doi:10.1016/j.febslet.2004.06.095 · Cited by 110 · see citing works
Mechanism of salvianolic acid B neuroprotection against ischemia/reperfusion induced cerebral injury
Fan, Y., Luo, Q., Wei, J., Lin, R., Li, Y., Li, Y., Chen, Q., Lin, W., & Chen, Q. (2017) · Brain Research · doi:10.1016/j.brainres.2017.11.027 · Cited by 103 · see citing works
Self-citationDock4 is regulated by RhoG and promotes Rac-dependent cell migration
Hiramoto, K., Negishi, M., & Katoh, H. (2006) · Experimental Cell Research · doi:10.1016/j.yexcr.2006.09.006 · Cited by 92 · see citing works
Su, J., Guo, K., Huang, M., Liu, Y., Zhang, J., Sun, L., Li, D., Pang, K., Wang, G., Chen, L., et al. (2019) · Frontiers in Pharmacology · doi:10.3389/fphar.2019.00906 · Cited by 89 · see citing works
Self-citationCellular signaling of Dock family proteins in neural function
Miyamoto, Y., & Yamauchi, J. (2009) · Cellular Signalling · doi:10.1016/j.cellsig.2009.09.036 · Cited by 85 · see citing works
MOCA Induces Membrane Spreading by Activating Rac1
Namekata, K., Enokido, Y., Iwasawa, K., & Kimura, H. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.m311275200 · Cited by 84 · see citing works
Self-citationLiu, G., Jiang, Y., Wang, P., Feng, R., Jiang, N., Chen, X., Song, H., & Chen, Z. (2011) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.2011.07547.x · Cited by 83 · see citing works
Dock protein family in brain development and neurological disease
Shi, L. (2013) · Communicative & Integrative Biology · doi:10.4161/cib.26839 · Cited by 83 · see citing works
Inhibition of APP Trafficking by Tau Protein Does Not Increase the Generation of Amyloid‐β Peptides
Goldsbury, C., Mocanu, M., Thies, E., Kaether, C., Haass, C., Keller, P., Biernat, J., Mandelkow, E., & Mandelkow, E. (2006) · Traffic · doi:10.1111/j.1600-0854.2006.00434.x · Cited by 82 · see citing works
Phosphorylation and activation of Bub1 on unattached chromosomes facilitate the spindle checkpoint
Chen, R. (2004) · The EMBO Journal · doi:10.1038/sj.emboj.7600308 · Cited by 76 · see citing works
Huttunen, H. J., Guénette, S. Y., Peach, C., Greco, C., Xia, W., Kim, D. Y., Barren, C., Tanzi, R. E., & Kovacs, D. M. (2007) · Journal of Biological Chemistry · doi:10.1074/jbc.m702951200 · Cited by 72 · see citing works
Loss of Modifier of Cell Adhesion Reveals a Pathway Leading to Axonal Degeneration
Chen, Q., Peto, C. A., Shelton, G. D., Mizisin, A. P., Sawchenko, P. E., & Schubert, D. A. (2009) · Journal of Neuroscience · doi:10.1523/jneurosci.3985-08.2009 · Cited by 65 · see citing works
Self-citationAlzheimer's disease meets the ubiquitin–proteasome system
Song, S., & Jung, Y. (2004) · Trends in Molecular Medicine · doi:10.1016/j.molmed.2004.09.005 · Cited by 65 · see citing works
Dock4 regulates dendritic development in hippocampal neurons.
Ueda, S., Fujimoto, S., Hiramoto, K., Negishi, M., & Katoh, H. (2008) · Journal of Neuroscience Research · doi:10.1002/jnr.21763 · Cited by 61 · see citing works
The Role of Presenilin and its Interacting Proteins in the Biogenesis of Alzheimer’s Beta Amyloid
Verdile, G., Gandy, S., & Martins, R. N. (2006) · Neurochemical Research · doi:10.1007/s11064-006-9131-x · Cited by 60 · see citing works
Dock GEFs and their therapeutic potential: Neuroprotection and axon regeneration
Namekata, K., Kimura, A., Kawamura, K., Harada, C., & Harada, T. (2014) · Progress in Retinal and Eye Research · doi:10.1016/j.preteyeres.2014.06.005 · Cited by 57 · see citing works
Huttunen, H. J., Peach, C., Bhattacharyya, R., Barren, C., Pettingell, W. H., Hutter‐Paier, B., Windisch, M., Berezovska, O., & Kovacs, D. M. (2009) · The FASEB Journal · doi:10.1096/fj.09-134999 · Cited by 56 · see citing works
Conde, C., Osswald, M., Barbosa, J., Moutinho‐Santos, T., Pinheiro, D., Guimarães, S., Matos, I., Maiato, H., & Sunkel, C. E. (2013) · The EMBO Journal · doi:10.1038/emboj.2013.109 · Cited by 50 · see citing works
Dock3 interaction with a glutamate-receptor NR2D subunit protects neurons from excitotoxicity
Bai, N., Hayashi, H., Aida, T., Namekata, K., Harada, T., Mishina, M., & Tanaka, K. (2013) · Molecular Brain · doi:10.1186/1756-6606-6-22 · Cited by 48 · see citing works
Modifier of Cell Adhesion Regulates N-Cadherin-Mediated Cell-Cell Adhesion and Neurite Outgrowth
Chen, Q., Chen, T., Letourneau, P. C., Costa, L. D. F., & Schubert, D. A. (2005) · Journal of Neuroscience · doi:10.1523/jneurosci.3692-04.2005 · Cited by 47 · see citing works
Self-citationHasegawa, H., Liu, L., Tooyama, I., Murayama, S., & Nishimura, M. (2014) · Nature Communications · doi:10.1038/ncomms4917 · Cited by 47 · see citing works
Rho GTPases in neurodegeneration diseases
DeGeer, J., & Lamarche-Vane, N. (2013) · Experimental Cell Research · doi:10.1016/j.yexcr.2013.06.016 · Cited by 46 · see citing works
Regulation of dendrite growth by the Cdc42 activator Zizimin1/Dock9 in hippocampal neurons
Kuramoto, K., Negishi, M., & Katoh, H. (2009) · Journal of Neuroscience Research · doi:10.1002/jnr.21997 · Cited by 46 · see citing works
The emerging role of guanine nucleotide exchange factors in ALS and other neurodegenerative diseases
Droppelmann, C. A., Campos‐Melo, D., Volkening, K., & Strong, M. J. (2014) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2014.00282 · Cited by 41 · see citing works
Program, T. V. M. V., Bone, W. P., Siewert, K. M., Jha, A., Klarin, D., Damrauer, S. M., Chang, K.-M., Tsao, P. S., Assimes, T. L., Ritchie, M. D., et al. (2021) · Alzheimer's Research & Therapy · doi:10.1186/s13195-021-00773-z · Cited by 41 · see citing works
Bai, Y., Xiang, X., Liang, C., & Shi, L. (2015) · BioMed Research International · doi:10.1155/2015/632450 · Cited by 40 · see citing works
Proteasome-mediated effects on amyloid precursor protein processing at the γ-secretase site
Flood, F., MURPHY, S., Cowburn, R. F., Lannfelt, L., Walker, B., & Johnston, J. A. (2005) · Biochemical Journal · doi:10.1042/bj20041145 · Cited by 40 · see citing works
ILL‐Raga, G., Tajes, M., Busquets-García, A., Ramos‐Fernández, E., Vargas, L. M., Bosch-Morató, M., Guivernau, B., Valls-Comamala, V., Eraso‐Pichot, A., Guix, F. X., et al. (2015) · Antioxidants and Redox Signaling · doi:10.1089/ars.2014.6080 · Cited by 36 · see citing works
The DOCK Protein Sponge Binds to ELMO and Functions in Drosophila Embryonic CNS Development
Biersmith, B. H., Liu, Z., Bauman, K., & Geisbrecht, E. R. (2011) · PLoS ONE · doi:10.1371/journal.pone.0016120 · Cited by 28 · see citing works
Thompson, A. P., Bitsina, C., Gray, J. L., von Delft, F., & Brennan, P. E. (2021) · Journal of Biological Chemistry · doi:10.1016/j.jbc.2021.100521 · Cited by 21 · see citing works
Tachi, N., Hashimoto, Y., & Matsuoka, M. (2012) · Biochemical Journal · doi:10.1042/bj20100993 · Cited by 20 · see citing works
Dock3 Participate in Epileptogenesis Through rac1 Pathway in Animal Models
Li, J., Mi, X., Chen, L., Jiang, G., Wang, N., Zhang, Y., Deng, W., Wang, Z., Chen, G., & Wang, X. (2015) · Molecular Neurobiology · doi:10.1007/s12035-015-9406-9 · Cited by 19 · see citing works
Lefort, R. (2015) · Neurotherapeutics · doi:10.1007/s13311-014-0328-4 · Cited by 17 · see citing works
Cell adhesion protein decreases cell motion: Statistical characterization of locomotion activity
Diambra, L. A., Cintra, L. C., Chen, Q., Schubert, D., & Costa, L. D. F. (2005) · Physica A Statistical Mechanics and its Applications · doi:10.1016/j.physa.2005.10.006 · Cited by 16 · see citing works
Self-citationThe relationship between DNA methylation andReprimogene expression in gastric cancer cells
Lai, J., Wang, H., Luo, Q., Huang, S., Lin, S., Zheng, Y., & Chen, Q. (2017) · Oncotarget · doi:10.18632/oncotarget.21296 · Cited by 15 · see citing works
Self-citationEDEM1 Regulates Amyloid Precursor Protein (APP) Metabolism and Amyloid-β Production
Nowakowska-Gołacka, J., Czapiewska, J., Sominka, H., Sowa-Rogozińska, N., & Słomińska-Wojewódzka, M. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms23010117 · Cited by 14 · see citing works
Guix, F. X., Sartório, C. L., & ILL‐Raga, G. (2019) · Journal of Alzheimer s Disease Reports · doi:10.3233/adr-180089 · Cited by 13 · see citing works
Myre, M. A., Washicosky, K. J., Moir, R. D., Tesco, G., Tanzi, R. E., & Wasco, W. (2008) · Cellular Signalling · doi:10.1016/j.cellsig.2008.12.008 · Cited by 13 · see citing works
Effect of cell density on intracellular levels of the Alzheimer's amyloid precursor protein
Rebelo, S., Henriques, A. G., Silva, E. F. D. C. E., & Silva, O. A. B. D. C. E. (2004) · Journal of Neuroscience Research · doi:10.1002/jnr.20091 · Cited by 13 · see citing works
Avar, M., Heinzer, D., Thackray, A. M., Liu, Y., Hruška-Plocháň, M., Sellitto, S., Schaper, E., Pease, D., Yin, J., Lakkaraju, A. K., et al. (2022) · The EMBO Journal · doi:10.15252/embj.2022112338 · Cited by 12 · see citing works
Redox Pioneer: Professor Hideo Kimura
Lefer, D. J. (2018) · Antioxidants and Redox Signaling · doi:10.1089/ars.2018.7618 · Cited by 12 · see citing works
Namekata, K., Tsuji, N., Guo, X., Nishijima, E., Honda, S., Kitamura, Y., Yamasaki, A., Kishida, M., Takeyama, J., Ishikawa, H., et al. (2023) · Cell Death Discovery · doi:10.1038/s41420-023-01460-8 · Cited by 8 · see citing works
Liu, C., Zhao, Y., Dao, J.-J., Zhang, W., Liu, J., Ma, Y.-K., Qiao, C.-M., Cui, C., Chen, S., Shen, Y., et al. (2025) · Neurotherapeutics · doi:10.1016/j.neurot.2025.e00739 · Cited by 5 · see citing works
Activation of GTPases by Dock180 Family of Proteins
Lu, M., & Ravichandran, K. S. (2005) · Springer eBooks · doi:10.1007/1-4020-3462-8_4 · Cited by 2 · see citing works
Nishimura, M., Watanabe, N., Hibino, E., Nakano, M., Mitsuishi, Y., Liu, L., & Sugi, T. (2020) · Elsevier eBooks · doi:10.1016/b978-0-12-815868-5.00019-0 · Cited by 1 · see citing works
Namekata, K. (2014) · Springer eBooks · doi:10.1007/978-4-431-54965-9_23 · Cited by 1 · see citing works
Hamel, B. (2019) · Carolina Digital Repository (University of North Carolina at Chapel Hill) · doi:10.17615/kmq6-qg97 · Cited by 1 · see citing works
Whole Exome Analysis of Early Onset Alzheimer's Disease
Pericak‐Vance, M. A. (2013) · doi:10.21236/ada602412
Non-Maxwellian velocity distribution and anomalous diffusion of {\it in vitro} kidney cellsPreprint
Diambra, L. A., Cintra, L. C., Schubert, D., & Costa, L. D. F. (2005) · arXiv (Cornell University) · doi:10.48550/arxiv.q-bio/0503013
Self-citationThe Dock Family of Atypical Guanine Nucleotide Exchange Factors: Regulation by ELMO1 and RhoG
Holley, C. P. (2019) · Carolina Digital Repository (University of North Carolina at Chapel Hill) · doi:10.17615/m95n-qm88
Ubiquitin and Intracellular Aggregation
Song, S., & Jung, Y. (2003) · Springer eBooks · doi:10.1007/978-1-4757-5890-0_16
Bone, W. P., Siewert, K. M., Jha, A., Klarin, D. M., Damrauer, S. M., Chang, K.-M., Tsao, P. S., Assimes, T. L., Ritchie, M. D., & Voight, B. F. (2021) · Figshare · doi:10.6084/m9.figshare.13719193
- Authors
- Chen, Q., Kimura, H., & Schubert, D.
- Affiliations
- Salk Institute for Biological Studies (US)
- National Center of Neurology and Psychiatry (JP)
- Corresponding author
- Schubert, David
- Venue
- The Journal of Cell Biology
- Publisher
- Rockefeller University Press
- Published
- 2002-07-01
- Volume
- 158
- Issue
- 1
- Pages
- 79-89
- ISSN
- 0021-9525 (ISSN-L)
- 1540-8140
- PMC
- PMC2173011
- OpenAlex
- W2014633008
- Cited by
- 63
- References
- 66
- Citations by year
- 2025: 1 · 2023: 1 · 2022: 1 · 2021: 4 · 2020: 1 · 2019: 4 · 2018: 2 · 2017: 2 · 2016: 1 · 2015: 4 · 2014: 4 · 2013: 5 · 2012: 1
- FWCI
- 3.00
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- The Journal of Cell Biology (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion, cc-by-nc-sa)
- PubMed Central (publishedVersion, cc-by-nc-sa)
- PubMed (publishedVersion)
- Funders
- Alzheimer's Association
- National Institutes of Health
- Topics
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Keywords
- Montreal Cognitive Assessment, amyloid precursor protein, APP processing, proteasomal degradation, cell adhesion, presenilin, Alzheimer's disease, DOCK180, proteasome inhibitors
- MeSH terms
- Animals, Bacterial Proteins, Cell Adhesion, Cell Line, Cysteine Endopeptidases, Dose-Response Relationship, Drug, Enzyme-Linked Immunosorbent Assay, Gene Expression Regulation, Laminin, Microscopy, Fluorescence, Multienzyme Complexes, Neurons, Phenotype, Time Factors, Transfection, Tumor Cells, Cultured, Blotting, Northern, Blotting, Western, Amyloid beta-Peptides, Amyloid beta-Protein Precursor, Microscopy, Confocal, Reverse Transcriptase Polymerase Chain Reaction, Proteasome Endopeptidase Complex, Rats
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