Heat Shock Protein 90 Regulates the Metaphase-Anaphase Transition in a Polo-Like Kinase-Dependent Manner

de Cárcer, Guillermo

doi:10.1158/0008-5472.can-03-2214

Cited by 66Microtubule and mitosis dynamicsHeat shock proteins researchCancer-related Molecular Pathways

Heat Shock Protein 90 Regulates the Metaphase-Anaphase Transition in a Polo-Like Kinase-Dependent Manner

de Cárcer, Guillermo·2004·Cancer Research

DOI 10.1158/0008-5472.can-03-2214

Published version of a preprint

Open this paper in CoChat — free account

Abstract

We have shown previously that the molecular chaperone heat shock protein 90 (Hsp90) is required for a proper centrosome function. Indeed, this Hsp90 function seems to be reflected in Polo-like kinase stability. Inhibition of Hsp90 in HeLa cells results in cell cycle arrest either in G2 stage or at the metaphase-anaphase transition. Here, we show that this inhibition leads to inactivation of the anaphase-promoting complex or cyclosome by both dephosphorylation and induction of the spindle assembly checkpoint. Hsp90 inhibition compromises two of the main mitotic kinases, Polo-like kinase 1 (Plk1) and cdc2. Interestingly, this mitotic arrest does not occur in certain tumor cell lines where Hsp90 and Plk1 are not associated. Those cells are able to process mitosis successfully and have an active Plk1 despite Hsp90 inactivation. Therefore, it seems that Hsp90 regulates completion of mitosis depending on its association with Plk1.

Integrity signals

Registry

Crossref · 10.1158/0008-5472.can-03-2214

Cites

54 of 54 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?

Hsp90 is indispensable for appropriate regulation of cell cycle progression in many organisms.
“Among Hsp90's many roles in the cell, it is indispensable for appropriate regulation of cell cycle progression in many organisms.”
From Cdc28 provides a molecular link between Hsp90, morphogenesis, and cell cycle progression inCandida albicans (2012) · cites this paper as de Carcer, 2004
Plk1, the mammalian homologue of Cdc5, is an Hsp90 client protein, and Cdc5 interacts with an Hsp90 cochaperone, Cdc37, in S. cerevisiae.
“This is intriguing, as Plk1, the mammalian homologue of Cdc5, is an Hsp90 client protein, and Cdc5 interacts with an Hsp90 cochaperone, Cdc37, in S. cerevisiae (de Carcer et al., 2001; de Carcer, 2004; Mort-Bontemps-Soret et al., 2002).”
From Cdc28 provides a molecular link between Hsp90, morphogenesis, and cell cycle progression inCandida albicans (2012) · cites this paper as de Carcer, 2004

The hallmarks of cancer
Hanahan, D., & Weinberg, R. A. (2000) · Cell · doi:10.1016/s0092-8674(00)81683-9 · Cited by 29,219 · see citing works
Mutations of mitotic checkpoint genes in human cancers
Cahill, D. P., Christoph Lengauer, C., Yu, J., Riggins, G. J., Willson, J. K. V., Markowitz, S. D., Kinzler, K. W., & Vogelstein, B. (1998) · Nature · doi:10.1038/32688 · Cited by 1,485 · see citing works
Biochemical and Cellular Effects of Roscovitine, a Potent and Selective Inhibitor of the Cyclin‐Dependent Kinases cdc2, cdk2 and cdk5
Meijer, L., Borgne, A., Mulner, O., Chong, J. P. J., Blow, J. J., Inagaki, N., Inagaki, M., Delcros, J., & Moulinoux, J. (1997) · European Journal of Biochemistry · doi:10.1111/j.1432-1033.1997.t01-2-00527.x · Cited by 1,352 · see citing works
A 20s complex containing CDC27 and CDC16 catalyzes the mitosis-specific conjugation of ubiquitin to cyclin B
King, R. W., Peters, J., Tugendreich, S., Rolfe, M., Hieter, P., & Kirschner, M. W. (1995) · Cell · doi:10.1016/0092-8674(95)90338-0 · Cited by 956 · see citing works
Inhibition of Cyclin‐Dependent Kinases by Purine Analogues
de Azevedo, W. F., Leclerc, S., Meijer, L., Havlı́ček, L., Strnad, M., & Kim, S. (1997) · European Journal of Biochemistry · doi:10.1111/j.1432-1033.1997.0518a.x · Cited by 733 · see citing works
Antibody microinjection reveals an essential role for human polo-like kinase 1 (Plk1) in the functional maturation of mitotic centrosomes.
Lane, H. A., & Nigg, E. A. (1996) · The Journal of Cell Biology · doi:10.1083/jcb.135.6.1701 · Cited by 695 · see citing works
Monoclonal antibodies to mitotic cells.
Davis, F. M., Tsao, T. Y., Fowler, S. K., & Rao, P. N. (1983) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.80.10.2926 · Cited by 602 · see citing works
The checkpoint protein MAD2 and the mitotic regulator CDC20 form a ternary complex with the anaphase-promoting complex to control anaphase initiationPreprint
Fang, G., Yu, H., & Kirschner, M. W. (1998) · Genes & Development · doi:10.1101/gad.12.12.1871 · Cited by 597 · see citing works
Polo, a mitotic mutant of Drosophila displaying abnormal spindle poles
Sunkel, C. E., & Glover, D. M. (1988) · Journal of Cell Science · doi:10.1242/jcs.89.1.25 · Cited by 563 · see citing works
HSP90 as a new therapeutic target for cancer therapy: the story unfolds
Maloney, A., & Workman, P. (2002) · Expert Opinion on Biological Therapy · doi:10.1517/14712598.2.1.3 · Cited by 531 · see citing works
Control of Cyclin Ubiquitination by CDK-Regulated Binding of Hct1 to the Anaphase Promoting Complex
Zachariae, W., Schwab, M., Nasmyth, K., & Seufert, W. (1998) · Science · doi:10.1126/science.282.5394.1721 · Cited by 511 · see citing works
Direct Binding of CDC20 Protein Family Members Activates the Anaphase-Promoting Complex in Mitosis and G1
Fang, G., Yu, H., & Kirschner, M. W. (1998) · Molecular Cell · doi:10.1016/s1097-2765(00)80126-4 · Cited by 486 · see citing works
The Polo‐like kinase Cdc5p and the WD‐repeat protein Cdc20p/fizzy are regulators and substrates of the anaphase promoting complex in Saccharomyces cerevisiae
Shirayama, M., Zachariae, W., Ciosk, R., & Nasmyth, K. (1998) · The EMBO Journal · doi:10.1093/emboj/17.5.1336 · Cited by 483 · see citing works
Polo-like kinase (Plk)1 depletion induces apoptosis in cancer cells
Liu, X., & Erikson, R. L. (2003) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1031523100 · Cited by 474 · see citing works
Polo-like kinase-1 is a target of the DNA damage checkpoint
Smits, V. A. J., Klompmaker, R., Arnaud, L., Rijksen, G., Nigg, E. A., & Medema, R. H. (2000) · Nature Cell Biology · doi:10.1038/35023629 · Cited by 442 · see citing works
Polo-like kinases: a team that plays throughout mitosisPreprint
Glover, D. M., Hagan, I., & Tavares, Á. A. (1998) · Genes & Development · doi:10.1101/gad.12.24.3777 · Cited by 427 · see citing works
polo encodes a protein kinase homolog required for mitosis in Drosophila.Preprint
Llamazares, S., Moreira, A., Tavares, Á. A., Girdham, C. H., Spruce, B. A., González, C., Karess, R. E., Glover, D. M., & Sunkel, C. E. (1991) · Genes & Development · doi:10.1101/gad.5.12a.2153 · Cited by 400 · see citing works
Polo-like kinase 1 phosphorylates cyclin B1 and targets it to the nucleus during prophase
Toyoshima, F., Taniguchi, E., Shinya, N., Iwamatsu, A., & Nishida, E. (2001) · Nature · doi:10.1038/35065617 · Cited by 366 · see citing works
CDC27Hs colocalizes with CDC16Hs to the centrosome and mitotic spindle and is essential for the metaphase to anaphase transition
Tugendreich, S., Tomkiel, J. E., Earnshaw, W. C., & Hieter, P. (1995) · Cell · doi:10.1016/0092-8674(95)90336-4 · Cited by 364 · see citing works
Phosphorylation of the Cohesin Subunit Scc1 by Polo/Cdc5 Kinase Regulates Sister Chromatid Separation in Yeast
Alexandru, G., Uhlmann, F., Mechtler, K., Poupart, M., & Nasmyth, K. (2001) · Cell · doi:10.1016/s0092-8674(01)00362-2 · Cited by 351 · see citing works
The essential mitotic peptidyl-prolyl isomerase Pin1 binds and regulates mitosis-specific phosphoproteinsPreprint
Shen, M., Stukenberg, P. T., Kirschner, M. W., & Lu, K.-P. (1998) · Genes & Development · doi:10.1101/gad.12.5.706 · Cited by 341 · see citing works
Visualization of Mad2 Dynamics at Kinetochores, along Spindle Fibers, and at Spindle Poles in Living Cells
Howell, B. J., Hoffman, D. B., Fang, G., Murray, A. W., & Salmon, E. D. (2000) · The Journal of Cell Biology · doi:10.1083/jcb.150.6.1233 · Cited by 327 · see citing works
PKA and MPF-Activated Polo-like Kinase Regulate Anaphase-Promoting Complex Activity and Mitosis Progression
Kotani, S., Tugendreich, S., Fujii, M., Jorgensen, P.-M., Watanabe, N., Höög, C., Hieter, P., & Todokoro, K. (1998) · Molecular Cell · doi:10.1016/s1097-2765(00)80037-4 · Cited by 301 · see citing works
Inhibition of signal transduction by the Hsp90 inhibitor 17-allylamino-17-demethoxygeldanamycin results in cytostasis and apoptosis.
Hostein, I., Robertson, D. M., Di-Stefano, F., Workman, P., & Clarke, P. A. (2001) · PubMed · Cited by 284 · see citing works
Cloning of cDNAs for M-phase phosphoproteins recognized by the MPM2 monoclonal antibody and determination of the phosphorylated epitope.
WESTENDORF, J. M., Rao, P. N., & Gerace, L. (1994) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.91.2.714 · Cited by 255 · see citing works
Mammalian p55CDC Mediates Association of the Spindle Checkpoint Protein Mad2 with the Cyclosome/Anaphase-promoting Complex, and is Involved in Regulating Anaphase Onset and Late Mitotic Events
Kallio, M. J., Weinstein, J., Daum, J. R., Burke, D. J., & Gorbsky, G. J. (1998) · The Journal of Cell Biology · doi:10.1083/jcb.141.6.1393 · Cited by 240 · see citing works
Systematic identification of mitotic phosphoproteins
Stukenberg, P. T., Lustig, K. D., McGarry, T. J., King, R. W., Kuang, J., & Kirschner, M. W. (1997) · Current Biology · doi:10.1016/s0960-9822(06)00157-6 · Cited by 220 · see citing works
The polo‐like kinase Plx1 is required for M phase exit and destruction of mitotic regulators in Xenopus egg extracts
Descombes, P., & Nigg, E. A. (1998) · The EMBO Journal · doi:10.1093/emboj/17.5.1328 · Cited by 211 · see citing works
Reversible phosphorylation controls the activity of cyclosome-associated cyclin-ubiquitin ligase.
Lahav‐Baratz, S., Sudakin, V., RUDERMAN, J. V., & Hershko, A. (1995) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.92.20.9303 · Cited by 197 · see citing works
Identification of novel M phase phosphoproteins by expression cloning.
Matsumoto-Taniura, N., Pirollet, F., Monroe, R. R., Gerace, L., & WESTENDORF, J. M. (1996) · Molecular Biology of the Cell · doi:10.1091/mbc.7.9.1455 · Cited by 188 · see citing works
Downregulation of human polo-like kinase activity by antisense oligonucleotides induces growth inhibition in cancer cells
Spänkuch, B., Wolf, G., Solbach, C., Loibl, S., Knecht, R., Stegmüller, M., von Minckwitz, G., Kaufmann, M., & Strebhardt, K. (2002) · Oncogene · doi:10.1038/sj.onc.1205412 · Cited by 149 · see citing works
Inhibition of heat shock protein 90 function by ansamycins causes the morphological and functional differentiation of breast cancer cells.
Münster, P. N., Srethapakdi, M., Moasser, M. M., & Rosen, N. X. (2001) · PubMed · Cited by 145 · see citing works
Mad2 transiently associates with an APC/p55Cdc complex during mitosis
Wassmann, K., & Benezra, R. (1998) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.95.19.11193 · Cited by 129 · see citing works
Cell Cycle-regulated Expression, Phosphorylation, and Degradation of p55Cdc
Weinstein, J. (1997) · Journal of Biological Chemistry · doi:10.1074/jbc.272.45.28501 · Cited by 129 · see citing works
Inhibition of Hsp90 function by ansamycins causes retinoblastoma gene product-dependent G1 arrest.
Srethapakdi, M., Liu, F., Tavorath, R., & Rosen, N. X. (2000) · PubMed · Cited by 126 · see citing works
Hsp90 is a core centrosomal component and is required at different stages of the centrosome cycle in Drosophila and vertebrates
Lange, B. M. H., Bachi, A., Wilm, M., & González, C. (2000) · The EMBO Journal · doi:10.1093/emboj/19.6.1252 · Cited by 123 · see citing works
Mutations in the Plk gene lead to instability of Plk protein in human tumour cell lines
Simizu, S., & Osada, H. (2000) · Nature Cell Biology · doi:10.1038/35041102 · Cited by 120 · see citing works
Human Prk Is a Conserved Protein Serine/Threonine Kinase Involved in Regulating M Phase Functions
Ouyang, B., Pan, H., Lu, L., et al. (1997) · Journal of Biological Chemistry · doi:10.1074/jbc.272.45.28646 · Cited by 111 · see citing works
Geldanamycin Induces Heat Shock Protein Expression Through Activation of HSF1 in K562 Erythroleukemic Cells
Kim, H. R., Kang, H. S., & Kim, H. D. (1999) · IUBMB Life · doi:10.1080/713803536 · Cited by 107 · see citing works
The Drosophila POLO kinase localises to multiple compartments of the mitotic apparatus and is required for the phosphorylation of MPM2 reactive epitopes
Logarinho, E., & Sunkel, C. E. (1998) · Journal of Cell Science · doi:10.1242/jcs.111.19.2897 · Cited by 103 · see citing works
Cell cycle transition under stress conditions controlled by vertebrate heat shock factors
Nakai, A., & Ishikawa, T. (2001) · The EMBO Journal · doi:10.1093/emboj/20.11.2885 · Cited by 92 · see citing works
Requirement of Hsp90 for centrosomal function reflects its regulation of Polo kinase stability
de Cárcer, G., do Carmo Avides, M., Lallena, M. J., Glover, D. M., & González, C. (2001) · The EMBO Journal · doi:10.1093/emboj/20.11.2878 · Cited by 90 · see citing works
In Vivo Release of Mitotic Silencing of Ribosomal Gene Transcription Does Not Give Rise to Precursor Ribosomal RNA Processing
Sirri, V., Roussel, P., & Hernandez‐Verdun, D. (2000) · The Journal of Cell Biology · doi:10.1083/jcb.148.2.259 · Cited by 88 · see citing works
Enhancement of paclitaxel-mediated cytotoxicity in lung cancer cells by 17-allylamino geldanamycin: in vitro and in vivo analysis
Nguyen, D. M., Lorang, D., Chen, G. A., Stewart, J. H., Tabibi, E., & Schrump, D. S. (2001) · The Annals of Thoracic Surgery · doi:10.1016/s0003-4975(01)02787-4 · Cited by 78 · see citing works
Heat-Shock Protein 90 (hsp90) Bindsin Vitroto Tubulin Dimer and Inhibits Microtubule Formation
Garnier, C., Barbier, P., Gilli, R. M., Lopez, C., Peyrot, V., & Briand, C. M. (1998) · Biochemical and Biophysical Research Communications · doi:10.1006/bbrc.1998.9319 · Cited by 78 · see citing works
Immunofluorescence colocalization of the 90-kDa heat-shock protein and microtubules in interphase and mitotic mammalian cells.
Redmond, T., Sánchez, E. R., Bresnick, E. H., et al. (1989) · PubMed · Cited by 59 · see citing works
Identification of a Complex between Centrin and Heat Shock Proteins in CSF-Arrested Xenopus Oocytes and Dissociation of the Complex Following Oocyte Activation
Uzawa, M., Grams, J. M., Madden, B. J., et al. (1995) · Developmental Biology · doi:10.1006/dbio.1995.1259 · Cited by 55 · see citing works
Genetic interactions between Hsp90 and the Cdc2 mitotic machineryin the fission yeast Schizosaccharomyces pombe
Muñoz, M. J., & Jiménez, J. (1999) · Molecular and General Genetics MGG · doi:10.1007/s004380050963 · Cited by 52 · see citing works
Sequence-dependent enhancement of paclitaxel toxicity in non–small cell lung cancer by 17-allylamino 17-demethoxygeldanamycin
Nguyen, D. M., Chen, A. C.-H., Mixon, A., et al. (1999) · Journal of Thoracic and Cardiovascular Surgery · doi:10.1016/s0022-5223(99)70061-9 · Cited by 38 · see citing works
Mutations in New Cell Cycle Genes That Fail to Complement a Multiply Mutant Third Chromosome of Drosophila
White‐Cooper, H., Cannena, M., González, C., et al. (1996) · Genetics · doi:10.1534/genetics.112.1097.test · Cited by 35 · see citing works
Different Constitutive Heat Shock Protein 70 Expression During Proliferation and Differentiation of Rat C6 Glioma Cells
Helmbrecht, K., & Rensing, L. (1999) · Neurochemical Research · doi:10.1023/a:1020933308947 · Cited by 25 · see citing works
Cell-cycle arrests and p53 accumulation induced by geldanamycin in human ovarian tumour cells
McIlwrath, A. J., Brunton, V. G., & Brown, R. E. (1996) · Cancer Chemotherapy and Pharmacology · doi:10.1007/s002800050407 · Cited by 25 · see citing works
The polo-like kinase Plx1 prevents premature inactivation of the APCFizzy-dependent pathway in the early Xenopus cell cycle
Brassac, T., Castro, A., Lorca, T., et al. (2000) · Oncogene · doi:10.1038/sj.onc.1203724 · Cited by 24 · see citing works
Mutations in New Cell Cycle Genes That Fail to Complement a Multiply Mutant Third Chromosome of Drosophila
White‐Cooper, H., Cannena, M., González, C., et al. (1996) · Genetics · doi:10.1093/genetics/144.3.1097 · Cited by 21 · see citing works

Flagged first, then by citations

Sorted by citations

Diverse Cellular Functions of the Hsp90 Molecular Chaperone Uncovered Using Systems Approaches
McClellan, A. J., Xia, Y., Deutschbauer, A. M., Davis, R. W., Gerstein, M., & Frydman, J. (2007) · Cell · doi:10.1016/j.cell.2007.07.036 · Cited by 474 · see citing works
Cdc28 provides a molecular link between Hsp90, morphogenesis, and cell cycle progression inCandida albicans
Senn, H., Shapiro, R. S., & Cowen, L. E. (2012) · Molecular Biology of the Cell · doi:10.1091/mbc.e11-08-0729 · Cited by 67 · see citing works
Large-scale cytological profiling for functional analysis of bioactive compounds
Woehrmann, M. H., Bray, W. M., Durbin, J. K., Nisam, S. C., Michael, A. K., Glassey, E., Stuart, J. M., & Lokey, R. S. (2013) · Molecular BioSystems · doi:10.1039/c3mb70245f · Cited by 62 · see citing works

A review of Plks: Thinking outside the (polo) box
Korns, J., Liu, X., & Takiar, V. (2022) · Molecular Carcinogenesis · doi:10.1002/mc.23388 · Cited by 17 · see citing works
Progress in the Discovery of Polo-like Kinase Inhibitors
McInnes, C., Mezna, M., & Fischer, P. M. (2005) · Current Topics in Medicinal Chemistry · doi:10.2174/1568026053507660 · Cited by 111 · see citing works
Preclinical Research and Early Clinical Research of Polo-like Kinase 1 Inhibitors
Wang, G. (2011) · Pharmaceutical and Clinical Research
A Molecular Docking Study of Aristolactam Analogues against Polo-Box Domain (PBD) of Human Polo Like kinase-1 in Cancer Progression
Cheemanapalli, S., Pulaganti, M., Nagaraju, C., et al. (2014)
Polo-Like Kinase 1: Target and Regulator of Anaphase-Promoting Complex/Cyclosome–Dependent Proteolysis
Eckerdt, F., & Strebhardt, K. (2006) · Cancer Research · doi:10.1158/0008-5472.can-06-0358 · Cited by 77 · see citing works

Authors: de Cárcer, G.
Affiliations: Molecular Oncology Programme, Centro Nacional de Investigaciones Oncológicas, Madrid, Spain
Venue: Cancer Research
Publisher: American Association for Cancer Research (AACR)
Published: 2004-08-01
Volume: 64
Issue: 15
Pages: 5106-5112
ISSN: 0008-5472 (ISSN-L)
1538-7445
DOI: 10.1158/0008-5472.can-03-2214
OpenAlex: W2119237325
Cited by: 66
References: 54
Citations by year: 2026: 1 · 2025: 1 · 2024: 1 · 2023: 3 · 2022: 1 · 2021: 4 · 2020: 1 · 2019: 2 · 2018: 1 · 2017: 2 · 2016: 1 · 2015: 2 · 2014: 5 · 2013: 4 · 2012: 5
FWCI: 1.78
Type: journal article
Language: en
Open access: closed
Locations: Cancer Research (publishedVersion)
PubMed (publishedVersion)
Funders: European Molecular Biology Laboratory
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Microtubule and mitosis dynamics
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Heat shock proteins research
Health Sciences › Medicine › Oncology › Cancer-related Molecular Pathways
Keywords: HSP90, PLK1, metaphase-anaphase transition, anaphase-promoting complex, spindle assembly checkpoint, cdc2, mitotic arrest, HSP90 inhibition, protein stability, centrosome function, molecular chaperones, cancer cell lines
MeSH terms: Polo-Like Kinase 1, Anaphase, Gibberellins, HeLa Cells, Humans, Lung Neoplasms, Metaphase, Mitosis, Spindle Apparatus, Phosphorylation, Plant Growth Regulators, Protein Kinases, Proto-Oncogene Proteins, G2 Phase, CDC2 Protein Kinase, Protein Serine-Threonine Kinases, Cell Cycle Proteins, HSP90 Heat-Shock Proteins

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

Heat Shock Protein 90 Regulates the Metaphase-Anaphase Transition in a Polo-Like Kinase-Dependent Manner

Abstract

Integrity signals

Claims the paper makes

Claims other papers make about this one

Cites

Cited by

Related

Record

About these checks