Aurora kinases and protein phosphatase 1 mediate chromosome congression through regulation of CENP-E
Open accessAbstract
Opposing roles of Aurora kinases and protein phosphatase 1 (PP1) during mitosis have long been suggested. Here, we demonstrate that Aurora kinases A and B phosphorylate a conserved residue on the kinetochore motor CENP-E. PP1 binds CENP-E via a motif overlapping this phosphorylation site and binding is disrupted by Aurora phosphorylation. Phosphorylation of CENP-E by the Auroras is enriched at spindle poles, disrupting binding of PP1 and reducing CENP-E's affinity for individual microtubules. This phosphorylation is required for CENP-E-mediated towing of initially polar chromosomes toward the cell center. Kinetochores on such chromosomes cannot make subsequent stable attachment to spindle microtubules when dephosphorylation of CENP-E or rebinding of PP1 to CENP-E is blocked. Thus, an Aurora/PP1 phosphorylation switch modulates CENP-E motor activity as an essential feature of chromosome congression from poles and localized PP1 delivery by CENP-E to the outer kinetochore is necessary for stable microtubule capture by those chromosomes.
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
Cites
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?
Adjacent to T422 is a docking motif for type 1 phosphatase PP1γ, which blocks direct binding of Aurora kinases and allows Cenp-E to deliver PP1 to kinetochores, where it helps contribute to stable bi-orientation of chromosomes.
“Adjacent to T422 is a docking motif for type 1 phosphatase (PP1γ), which blocks the direct binding of Aurora kinases and allows Cenp-E to deliver PP1 to kinetochores, where it also helps contribute to the stable bi-orientation of chromosomes [53].”
From Regulatory mechanisms that control mitotic kinesins (2015) · cites this paper as [53]
The Results identify a PP1 docking motif overlapping T422, and the Introduction says CENP-E delivers PP1 to the outer kinetochore for stable biorientation. But the binding mechanism is reversed: the Results show that Aurora-mediated phosphorylation disrupts PP1 binding to CENP-E, not that the PP1 docking motif blocks direct binding of Aurora kinases. (LLM, conf=0.90)
Experimental — accuracy not yet measured
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
Hopfield, J. J. (1974) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.71.10.4135 · Cited by 1,594 · see citing works
Ditchfield, C., Johnson, V., Tighe, A., Ellston, R. P. A., Haworth, C., Johnson, T., Mortlock, A. A., Keen, N., & Taylor, S. S. (2003) · The Journal of Cell Biology · doi:10.1083/jcb.200208091 · Cited by 1,201 · see citing works
Cleveland, D. W., Mao, Y., & Sullivan, K. F. (2003) · Cell · doi:10.1016/s0092-8674(03)00115-6 · Cited by 1,003 · see citing works
Self-citationThe Conserved KMN Network Constitutes the Core Microtubule-Binding Site of the Kinetochore
Cheeseman, I. M., Chappie, J. S., Kubalek, E. W., & Desai, A. B. (2006) · Cell · doi:10.1016/j.cell.2006.09.039 · Cited by 996 · see citing works
Improving the photostability of bright monomeric orange and red fluorescent proteins
Shaner, N. C., Lin, M. Z., McKeown, M. R., Steinbach, P. A., Hazelwood, K. L., Davidson, M. W., & Tsien, R. Y. (2008) · Nature Methods · doi:10.1038/nmeth.1209 · Cited by 994 · see citing works
Harrington, E. A., Bebbington, D., Moore, J., Rasmussen, R. K., Ajose-Adeogun, A. O., Nakayama, T., Graham, J. A., Demur, C., Hercend, T., Diu‐Hercend, A., et al. (2004) · Nature Medicine · doi:10.1038/nm1003 · Cited by 971 · see citing works
Boveri revisited: chromosomal instability, aneuploidy and tumorigenesis
Holland, A. J., & Cleveland, D. W. (2009) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm2718 · Cited by 859 · see citing works
Self-citationChromosomal passengers: conducting cell division
Ruchaud, S., Carmena, M., & Earnshaw, W. C. (2007) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm2257 · Cited by 811 · see citing works
Tanaka, T. U., Rachidi, N., Janke, C., Pereira, G., Gálová, M., Schiebel, E., Stark, M. J. R., & Nasmyth, K. (2002) · Cell · doi:10.1016/s0092-8674(02)00633-5 · Cited by 714 · see citing works
Aurora-A — A guardian of poles
Marumoto, T., Zhang, D., & Saya, H. (2005) · Nature reviews. Cancer · doi:10.1038/nrc1526 · Cited by 698 · see citing works
Predicting coiled coils by use of pairwise residue correlations.
Berger, B., Wilson, D. B., Wolf, E., Tonchev, T., Milla, M. E., & Kim, P. S. (1995) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.92.18.8259 · Cited by 622 · see citing works
Phospho-Regulation of Kinetochore-Microtubule Attachments by the Aurora Kinase Ipl1p
Cheeseman, I. M., Anderson, S., Jwa, M., et al. (2002) · Cell · doi:10.1016/s0092-8674(02)00973-x · Cited by 616 · see citing works
Rieder, C. L., & Alexander, S. P. H. (1990) · The Journal of Cell Biology · doi:10.1083/jcb.110.1.81 · Cited by 480 · see citing works
A Processive Single-Headed Motor: Kinesin Superfamily Protein KIF1A
Okada, Y., & Hirokawa, N. (1999) · Science · doi:10.1126/science.283.5405.1152 · Cited by 468 · see citing works
The depolymerizing kinesin MCAK uses lattice diffusion to rapidly target microtubule ends
Helenius, J., Brouhard, G., Kalaidzidis, Y., Diez, S., & Howard, J. (2006) · Nature · doi:10.1038/nature04736 · Cited by 454 · see citing works
Yeast kinesin-8 depolymerizes microtubules in a length-dependent manner
Varga, V., Helenius, J., Tanaka, K., Hyman, A. A., Tanaka, T. U., & Howard, J. (2006) · Nature Cell Biology · doi:10.1038/ncb1462 · Cited by 445 · see citing works
Correcting improper chromosome–spindle attachments during cell division
Lampson, M. A., Renduchitala, K., Khodjakov, A. L., & Kapoor, T. M. (2004) · Nature Cell Biology · doi:10.1038/ncb1102 · Cited by 431 · see citing works
CENP-E is a plus end-directed kinetochore motor required for metaphase chromosome alignment
Wood, K. W., Sakowicz, R., Goldstein, L. S. B., & Cleveland, D. W. (1997) · Cell · doi:10.1016/s0092-8674(00)80419-5 · Cited by 431 · see citing works
Self-citationChromosomes Can Congress to the Metaphase Plate Before Biorientation
Kapoor, T. M., Lampson, M. A., Hergert, P. J., et al. (2006) · Science · doi:10.1126/science.1122142 · Cited by 429 · see citing works
Cheeseman, I. M., Niessen, S., Anderson, S., Barron, F. E., Yates, J. R., Oegema, K., & Desai, A. B. (2004) · Genes & Development · doi:10.1101/gad.1234104 · Cited by 413 · see citing works
Antitumor activity of MLN8054, an orally active small-molecule inhibitor of Aurora A kinase
Manfredi, M. G., Ecsedy, J., Meetze, K. A., Balani, S. K., Burenkova, O. V., Chen, W., Galvin, K. M., Hoar, K. M., Huck, J. J., Leroy, P. J., et al. (2007) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0608798104 · Cited by 412 · see citing works
Aurora Kinase Promotes Turnover of Kinetochore Microtubules to Reduce Chromosome Segregation Errors
Cimini, D., Wan, X., Hirel, C. B., & Salmon, E. D. (2006) · Current Biology · doi:10.1016/j.cub.2006.07.022 · Cited by 401 · see citing works
Yao, X., Abrieu, A., Zheng, Y., Sullivan, K. F., & Cleveland, D. W. (2000) · Nature Cell Biology · doi:10.1038/35019518 · Cited by 394 · see citing works
Self-citationMicrotubule interaction site of the kinesin motor
Woehlke, G., Ruby, A. K., Hart, C. L., Ly, B., Hom-Booher, N., & Vale, R. D. (1997) · Cell · doi:10.1016/s0092-8674(00)80329-3 · Cited by 386 · see citing works
Liu, D., Vleugel, M., Backer, C. B., Hori, T., Fukagawa, T., Cheeseman, I. M., & Lampson, M. A. (2010) · The Journal of Cell Biology · doi:10.1083/jcb.201001006 · Cited by 369 · see citing works
Aurora-A Kinase Maintains the Fidelity of Early and Late Mitotic Events in HeLa Cells
Marumoto, T., Honda, S., Hara, T., Nitta, M., Hirota, T., Kohmura, E., & Saya, H. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.m306275200 · Cited by 363 · see citing works
Case, R. B., Pierce, D. W., Hom-Booher, N., Hart, C. L., & Vale, R. D. (1997) · Cell · doi:10.1016/s0092-8674(00)80360-8 · Cited by 348 · see citing works
Unstable Kinetochore-Microtubule Capture and Chromosomal Instability Following Deletion of CENP-E
Putkey, F. R., Cramer, T., Morphew, M. K., Silk, A. D., Johnson, R. S., McIntosh, J. R., & Cleveland, D. W. (2002) · Developmental Cell · doi:10.1016/s1534-5807(02)00255-1 · Cited by 331 · see citing works
Self-citationPhosphoproteome analysis of the human mitotic spindle
Nousiainen, M., Silljé, H. H. W., Sauer, G., Nigg, E. A., & Körner, R. (2006) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0507066103 · Cited by 325 · see citing works
Docking Motif-Guided Mapping of the Interactome of Protein Phosphatase-1
Hendrickx, A., Beullens, M., Ceulemans, H., Abt, T. D., Eynde, A. V., Nicolaescu, E., Lesage, B., & Bollen, M. (2009) · Chemistry & Biology · doi:10.1016/j.chembiol.2009.02.012 · Cited by 314 · see citing works
Holland, A. J., Lan, W., Niessen, S., et al. (2010) · The Journal of Cell Biology · doi:10.1083/jcb.200911102 · Cited by 275 · see citing works
Self-citationEngineering the Processive Run Length of the Kinesin Motor
Thorn, K. S., Ubersax, J. A., & Vale, R. D. (2000) · The Journal of Cell Biology · doi:10.1083/jcb.151.5.1093 · Cited by 275 · see citing works
Weaver, B. A. A., Bonday, Z., Putkey, F. R., Kops, G. J. P. L., Silk, A. D., & Cleveland, D. W. (2003) · The Journal of Cell Biology · doi:10.1083/jcb.200303167 · Cited by 271 · see citing works
Self-citationFrancisco, L., Wang, W., & Chan, C. S. M. (1994) · Molecular and Cellular Biology · doi:10.1128/mcb.14.7.4731 · Cited by 267 · see citing works
Repo-Man recruits PP1γ to chromatin and is essential for cell viability
Trinkle‐Mulcahy, L., Andersen, J., Lam, Y. W., Moorhead, G. B. G., Mann, M., & Lamond, A. I. (2006) · The Journal of Cell Biology · doi:10.1083/jcb.200508154 · Cited by 257 · see citing works
Kunitoku, N., Sasayama, T., Marumoto, T., Zhang, D., Honda, S., Kobayashi, O., Hatakeyama, K., Ushio, Y., Saya, H., & Hirota, T. (2003) · Developmental Cell · doi:10.1016/s1534-5807(03)00364-2 · Cited by 248 · see citing works
Kinesin ATPase: rate-limiting ADP release
Hackney, D. D. (1988) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.85.17.6314 · Cited by 239 · see citing works
Yao, X., Anderson, K., & Cleveland, D. W. (1997) · The Journal of Cell Biology · doi:10.1083/jcb.139.2.435 · Cited by 232 · see citing works
Self-citationZečević, M., Catling, A. D., Eblen, S. T., Renzi, L., Hittle, J. C., Yen, T. J., Gorbsky, G. J., & Weber, M. J. (1998) · The Journal of Cell Biology · doi:10.1083/jcb.142.6.1547 · Cited by 219 · see citing works
Taylor, S. S., Hussein, D. M., Wang, Y., et al. (2001) · Journal of Cell Science · doi:10.1242/jcs.114.24.4385 · Cited by 212 · see citing works
Hoar, K. M., Chakravarty, A., Rabino, C., Wysong, D. R., Bowman, D., Roy, N., & Ecsedy, J. (2007) · Molecular and Cellular Biology · doi:10.1128/mcb.02364-06 · Cited by 207 · see citing works
Two different microtubule-based motor activities with opposite polarities in kinetochores
Hyman, A. A., & Mitchison, T. J. (1991) · Nature · doi:10.1038/351206a0 · Cited by 201 · see citing works
KNL1 and the CENP-H/I/K Complex Coordinately Direct Kinetochore Assembly in Vertebrates
Cheeseman, I. M., Hori, T., Fukagawa, T., & Desai, A. B. (2007) · Molecular Biology of the Cell · doi:10.1091/mbc.e07-10-1051 · Cited by 193 · see citing works
Centromeric Aurora-B Activation Requires TD-60, Microtubules, and Substrate Priming Phosphorylation
Rosasco, S. E., Lan, W., Khorasanizadeh, S., & Stukenberg, P. T. (2008) · Science · doi:10.1126/science.1148980 · Cited by 155 · see citing works
Self-citationAurora B kinase and protein phosphatase 1 have opposing roles in modulating kinetochore assembly
Emanuele, M. J., Lan, W., Jwa, M., Miller, S. A., Chan, C. S. M., & Stukenberg, P. T. (2008) · The Journal of Cell Biology · doi:10.1083/jcb.200710019 · Cited by 149 · see citing works
Self-citationRegulation of Saccharomyces cerevisiae kinetochores by the type 1 phosphatase Glc7pPreprint
Sassoon, I., Severin, F. F., Andrews, P. D., et al. (1999) · Genes & Development · doi:10.1101/gad.13.5.545 · Cited by 149 · see citing works
Mitotic Regulation of Microtubule Cross-Linking Activity of CENP-E Kinetochore Protein
Liao, H., Li, G., & Yen, T. J. (1994) · Science · doi:10.1126/science.8023161 · Cited by 146 · see citing works
Time-lapse Imaging Reveals Dynamic Relocalization of PP1γ throughout the Mammalian Cell Cycle
Trinkle‐Mulcahy, L., Andrews, P. D., Wickramasinghe, S. R., Sleeman, J., Prescott, A. R., Lam, Y. W., Lyon, C. E., Swedlow, J. R., & Lamond, A. I. (2003) · Molecular Biology of the Cell · doi:10.1091/mbc.e02-07-0376 · Cited by 145 · see citing works
Gestaut, D. R., Graczyk, B., Cooper, J. R., et al. (2008) · Nature Cell Biology · doi:10.1038/ncb1702 · Cited by 142 · see citing works
Kim, Y., Heuser, J. E., Waterman, C. M., & Cleveland, D. W. (2008) · The Journal of Cell Biology · doi:10.1083/jcb.200802189 · Cited by 142 · see citing works
Self-citationAneuploidy: a matter of bad connections
Cimini, D., & Degrassi, F. (2005) · Trends in Cell Biology · doi:10.1016/j.tcb.2005.06.008 · Cited by 141 · see citing works
Regulation of protein phosphatase‐1G from rabbit/skeletal muscle
Hubbard, M. J., & COHEN, P. (1989) · European Journal of Biochemistry · doi:10.1111/j.1432-1033.1989.tb15263.x · Cited by 129 · see citing works
Phosphorylation relieves autoinhibition of the kinetochore motor Cenp-E
Espeut, J., Gaussen, A., Bieling, P., Morin, V., Prieto, S., Fesquet, D., Surrey, T., & Abrieu, A. (2008) · Molecular Cell · doi:10.1016/j.molcel.2008.01.004 · Cited by 121 · see citing works
Cyclin-B1-mediated inhibition of excess separase is required for timely chromosome disjunction
Holland, A. J., & Taylor, S. S. (2006) · Journal of Cell Science · doi:10.1242/jcs.03083 · Cited by 113 · see citing works
Self-citationQuantitative proteomic analysis of purified yeast kinetochores identifies a PP1 regulatory subunitPreprint
Akiyoshi, B., Nelson, C. R., Ranish, J. A., & Biggins, S. (2009) · Genes & Development · doi:10.1101/gad.1865909 · Cited by 109 · see citing works
K-loop insertion restores microtubule depolymerizing activity of a “neckless” MCAK mutant
Ovechkina, Y., Wagenbach, M., & Wordeman, L. G. (2002) · The Journal of Cell Biology · doi:10.1083/jcb.200205089 · Cited by 102 · see citing works
Yucel, J. K., Marszalek, J. D., McIntosh, J. R., et al. (2000) · The Journal of Cell Biology · doi:10.1083/jcb.150.1.1 · Cited by 83 · see citing works
Yucel, J. K., Marszalek, J. D., McIntosh, J. R., et al. (2000) · The Journal of Cell Biology · doi:10.1083/jcb.150.1.1a · Cited by 21 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Sensing centromere tension: Aurora B and the regulation of kinetochore function
Lampson, M. A., & Cheeseman, I. M. (2011) · Trends in Cell Biology · doi:10.1016/j.tcb.2010.10.007 · Cited by 375 · see citing works
A PP1-PP2A phosphatase relay controls mitotic progression
Grallert, A., Boke, E., Hagting, A., Hodgson, B., Connolly, Y., Griffiths, J. R., Smith, D. L., Pines, J., & Hagan, I. M. (2015) · Nature · doi:10.1038/nature14019 · Cited by 188 · see citing works
Aurora at the pole and equator: overlapping functions of Aurora kinases in the mitotic spindle
Hochegger, H., Hégarat, N., & Pereira-Leal, J. B. (2013) · Open Biology · doi:10.1098/rsob.120185 · Cited by 112 · see citing works
Regulatory mechanisms that control mitotic kinesins
Yount, A. L., Zong, H., & Walczak, C. E. (2015) · Experimental Cell Research · doi:10.1016/j.yexcr.2014.12.015 · Cited by 39 · see citing works
“Adjacent to T422 is a docking motif for type 1 phosphatase (PP1γ), which blocks the direct binding of Aurora kinases and allows Cenp-E to deliver PP1 to kinetochores, where it also helps contribute to the stable bi-orientation of chromosomes [53].”
Background
- Authors
- Kim, Y., Holland, A. J., Lan, W., & Cleveland, D. W.
- Affiliations
- University of California San Diego (US)
- Corresponding author
- Cleveland, Don W.
- Venue
- Cell
- Publisher
- Elsevier BV
- Published
- 2010-08
- Volume
- 142
- Issue
- 3
- Pages
- 444-455
- ISSN
- 0092-8674 (ISSN-L)
- PMC
- PMC2921712
- OpenAlex
- W2162328639
- Cited by
- 233
- References
- 58
- Citations by year
- 2026: 4 · 2025: 4 · 2024: 11 · 2023: 11 · 2022: 6 · 2021: 8 · 2020: 11 · 2019: 20 · 2018: 11 · 2017: 13 · 2016: 19 · 2015: 22 · 2014: 20 · 2013: 17 · 2012: 31
- FWCI
- 10.20
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- www.elsevier.com/tdm/userlicense/1.0/ (tdm)
- www.elsevier.com/legal/tdmrep-license (tdm)
- www.elsevier.com/open-access/userlicense/1.0/ (vor, 1081 d)
- doi.org/10.15223/policy-017 (stm-asf)
- doi.org/10.15223/policy-037 (stm-asf)
- doi.org/10.15223/policy-012 (stm-asf)
- doi.org/10.15223/policy-029 (stm-asf)
- doi.org/10.15223/policy-004 (stm-asf)
- Locations
- Cell (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institute of General Medical Sciences (R37GM029513, GM 29513, R01GM029513)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Microtubule and mitosis dynamics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › DNA Repair Mechanisms
- Keywords
- Aurora kinases, protein phosphatase 1, CENP-E, chromosome congression, mitosis, kinetochore-microtubule attachment, phosphorylation, spindle poles, microtubule capture, outer kinetochore
- MeSH terms
- Amino Acid Sequence, Animals, Chromosomal Proteins, Non-Histone, Chromosomes, HeLa Cells, Humans, Microtubules, Spindle Apparatus, Molecular Sequence Data, Phosphorylation, Xenopus laevis, Sequence Alignment, Protein Serine-Threonine Kinases, Protein Structure, Tertiary, Kinetochores, Protein Phosphatase 1, Aurora Kinases
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
