Error message

No crossref credentials set for sci

Bora and the Kinase Aurora A Cooperatively Activate the Kinase Plk1 and Control Mitotic Entry

Science, 20 June 2008
Vol. 320, Issue 5883, p. 1655-1658
DOI: 10.1126/science.1157425

Bora and the Kinase Aurora A Cooperatively Activate the Kinase Plk1 and Control Mitotic Entry

  1. Akiko Seki1,
  2. Judith A. Coppinger2,
  3. Chang-Young Jang1,
  4. John R. Yates, III2,
  5. Guowei Fang1,*
  1. 1 Department of Biological Sciences, Stanford University, Stanford, CA 94305–5020, USA.
  2. 2 Department of Chemical Physiology, The Scripps Research Institute, La Jolla, CA 92037, USA.
  1. * To whom correspondence should be addressed. E-mail: gwfang{at}


A central question in the study of cell proliferation is, what controls cell-cycle transitions? Although the accumulation of mitotic cyclins drives the transition from the G2 phase to the M phase in embryonic cells, the trigger for mitotic entry in somatic cells remains unknown. We report that the synergistic action of Bora and the kinase Aurora A (Aur-A) controls the G2-M transition. Bora accumulates in the G2 phase and promotes Aur-A–mediated activation of Polo-like kinase 1 (Plk1), leading to the activation of cyclin-dependent kinase 1 and mitotic entry. Mechanistically, Bora interacts with Plk1 and controls the accessibility of its activation loop for phosphorylation and activation by Aur-A. Thus, Bora and Aur-A control mitotic entry, which provides a mechanism for one of the most important yet ill-defined events in the cell cycle.

  • Received for publication 6 March 2008.
  • Accepted for publication 21 May 2008.


A. Seki, J. A. Coppinger, C.-Y. Jang, J. R. Yates, and G. Fang, Bora and the Kinase Aurora A Cooperatively Activate the Kinase Plk1 and Control Mitotic Entry. Science 320, 1655-1658 (2008).

MASTL promotes cyclin B1 destruction by enforcing Cdc20-independent binding of cyclin B1 to the APC/C
E. Voets, and R. Wolthuis
Biology Open 4, 484-495 (15 April 2015)

Cdk1 phosphorylates SPAT-1/Bora to trigger PLK-1 activation and drive mitotic entry in C. elegans embryos
N. Tavernier, A. Noatynska, C. Panbianco, L. Martino, L. Van Hove, F. Schwager, T. Leger, M. Gotta, and L. Pintard
JCB 208, 661-669 (16 March 2015)

Autoinhibition and relief mechanism for Polo-like kinase 4
J. E. Klebba, D. W. Buster, T. A. McLamarrah, N. M. Rusan, and G. C. Rogers
Proc. Natl. Acad. Sci. USA 112, E657-E666 (17 February 2015)

A unique insertion in STARD9's motor domain regulates its stability
S. Senese, K. Cheung, Y.-C. Lo, A. A. Gholkar, X. Xia, J. A. Wohlschlegel, and J. Z. Torres
Mol. Biol. Cell 26, 440-452 (1 February 2015)

The Centrosome and Its Duplication Cycle
J. Fu, I. M. Hagan, and D. M. Glover
Cold Spring Harb. Perspect. Biol. 7, a015800-a015800 (1 February 2015)

TRAP1 Is Involved in BRAF Regulation and Downstream Attenuation of ERK Phosphorylation and Cell-Cycle Progression: A Novel Target for BRAF-Mutated Colorectal Tumors
V. Condelli, A. Piscazzi, L. Sisinni, D. S. Matassa, F. Maddalena, G. Lettini, V. Simeon, G. Palladino, M. R. Amoroso, S. Trino et al.
Cancer Res. 74, 6693-6704 (15 November 2014)

DNA-Damage Response during Mitosis Induces Whole-Chromosome Missegregation
S. F. Bakhoum, L. Kabeche, J. P. Murnane, B. I. Zaki, and D. A. Compton
Cancer Discovery 4, 1281-1289 (1 November 2014)

Polo kinase regulates the localization and activity of the chromosomal passenger complex in meiosis and mitosis in Drosophila melanogaster
M. Carmena, M. O. Lombardia, H. Ogawa, and W. C. Earnshaw
Open Biol 4, 140162-140162 (1 November 2014)

Interdomain allosteric regulation of Polo kinase by Aurora B and Map205 is required for cytokinesis
D. Kachaner, X. Pinson, K. B. El Kadhi, K. Normandin, L. Talje, H. Lavoie, G. Lepine, S. Carreno, B. H. Kwok, G. R. Hickson et al.
JCB 207, 201-211 (27 October 2014)

The role of mitotic kinases in coupling the centrosome cycle with the assembly of the mitotic spindle
G. Wang, Q. Jiang, and C. Zhang
J. Cell Sci. 127, 4111-4122 (1 October 2014)

Aurora-A Inhibition Offers a Novel Therapy Effective against Intracranial Glioblastoma
J. R. Van Brocklyn, J. Wojton, W. H. Meisen, D. A. Kellough, J. A. Ecsedy, B. Kaur, and N. L. Lehman
Cancer Res. 74, 5364-5370 (1 October 2014)

Centrosomes as signalling centres
C. Arquint, A.-M. Gabryjonczyk, and E. A. Nigg
Phil Trans R Soc B 369, 20130464-20130464 (5 September 2014)

Evidence toward a Dual Phosphatase Mechanism That Restricts Aurora A (Thr-295) Phosphorylation during the Early Embryonic Cell Cycle
Q. Kang, J. Srividhya, J. Ipe, and J. R. Pomerening
J Biol Chem 289, 17480-17496 (20 June 2014)

Bora and Aurora-A continue to activate Plk1 in mitosis
W. Bruinsma, L. Macurek, R. Freire, A. Lindqvist, and R. H. Medema
J. Cell Sci. 127, 801-811 (15 February 2014)

Molecular mechanism of Aurora A kinase autophosphorylation and its allosteric activation by TPX2
A. Zorba, V. Buosi, S. Kutter, N. Kern, F. Pontiggia, Y.-J. Cho, and D. Kern
elife 3, e02667-e02667 (1 January 2014)

Stathmin and microtubules regulate mitotic entry in HeLa cells by controlling activation of both Aurora kinase A and Plk1
V. C. Silva, and L. Cassimeris
Mol. Biol. Cell 24, 3819-3831 (15 December 2013)

Spatial control of mitotic commitment in fission yeast
I. M. Hagan, and A. Grallert
Biochm. Soc. Trans. 41, 1766-1771 (1 December 2013)

Pin1 acts as a negative regulator of the G2/M transition by interacting with the Aurora-A-Bora complex
Y.-C. Lee, J. Que, Y.-C. Chen, J.-T. Lin, Y.-C. Liou, P.-C. Liao, Y.-P. Liu, K.-H. Lee, L.-C. Lin, M. Hsiao et al.
J. Cell Sci. 126, 4862-4872 (1 November 2013)

FancJ regulates interstrand crosslinker induced centrosome amplification through the activation of polo-like kinase 1
J. Zou, F. Tian, J. Li, W. Pickner, M. Long, K. Rezvani, H. Wang, and D. Zhang
Biology Open 2, 1022-1031 (15 October 2013)

PDK1 Signaling Toward PLK1-MYC Activation Confers Oncogenic Transformation, Tumor-Initiating Cell Activation, and Resistance to mTOR-Targeted Therapy
J. Tan, Z. Li, P. L. Lee, P. Guan, M. Y. Aau, S. T. Lee, M. Feng, C. Z. Lim, E. Y. J. Lee, Z. N. Wee et al.
Cancer Discovery 3, 1156-1171 (1 October 2013)

Downregulation of Polo-Like Kinase 1 Induces Cellular Senescence in Human Primary Cells Through a p53-Dependent Pathway
H.-J. Kim, J. H. Cho, and J.-R. Kim
J Gerontol A Biol Sci Med Sci 68, 1145-1156 (1 October 2013)

Coordinating cell polarity and cell cycle progression: what can we learn from flies and worms?
A. Noatynska, N. Tavernier, M. Gotta, and L. Pintard
Open Biol 3, 130083-130083 (7 August 2013)

Ataxia Telangiectasia-mutated- and Rad3-related Protein Regulates the DNA Damage-induced G2/M Checkpoint through the Aurora A Cofactor Bora Protein
B. Qin, B. Gao, J. Yu, J. Yuan, and Z. Lou
J Biol Chem 288, 16139-16144 (31 May 2013)

Comparative Phosphoproteomic Analysis of Checkpoint Recovery Identifies New Regulators of the DNA Damage Response
V. A. Halim, M. Alvarez-Fernandez, Y. J. Xu, M. Aprelia, H. W. P. van den Toorn, A. J. R. Heck, S. Mohammed, and R. H. Medema
Sci Signal 6, rs9-rs9 (23 April 2013)

Basal aurora kinase B activity is sufficient for histone H3 phosphorylation in prophase
L.-T.-T. Le, H.-L. Vu, C.-H. Nguyen, and A. Molla
Biology Open 2, 379-386 (15 April 2013)

PCM1 recruits Plk1 to the pericentriolar matrix to promote primary cilia disassembly before mitotic entry
G. Wang, Q. Chen, X. Zhang, B. Zhang, X. Zhuo, J. Liu, Q. Jiang, and C. Zhang
J. Cell Sci. 126, 1355-1365 (15 March 2013)

Oscillation of APC/C activity during cell cycle arrest promotes centrosome amplification
S. L. Prosser, M. D. Samant, J. E. Baxter, C. G. Morrison, and A. M. Fry
J. Cell Sci. 125, 5353-5368 (15 November 2012)

Aurora Kinase A Drives MTOC Biogenesis but Does Not Trigger Resumption of Meiosis in Mouse Oocytes Matured In Vivo
P. Solc, V. Baran, A. Mayer, T. Bohmova, G. Panenkova-Havlova, A. Saskova, R. M. Schultz, and J. Motlik
Biol. Reprod. 87, 85-85 (11 October 2012)

Regulation of the Cell Division Cycle in Trypanosoma brucei
Z. Li, V. Baran, A. Mayer, T. Bohmova, G. Panenkova-Havlova, A. Saskova, R. M. Schultz, and J. Motlik
Eukaryot Cell 11, 1180-1190 (1 October 2012)

Furry Protein Promotes Aurora A-mediated Polo-like Kinase 1 Activation
M. Ikeda, S. Chiba, K. Ohashi, and K. Mizuno
J Biol Chem 287, 27670-27681 (10 August 2012)

A Highly Efficient Multifunctional Tandem Affinity Purification Approach Applicable to Diverse Organisms
H. Ma, J. R. McLean, L. F.-I. Chao, S. Mana-Capelli, M. Paramasivam, K. A. Hagstrom, K. L. Gould, and D. McCollum
MCP 11, 501-511 (1 August 2012)

Identification of a novel Wnt5a-CK1{varepsilon}-Dvl2-Plk1-mediated primary cilia disassembly pathway
K. H. Lee, Y. Johmura, L.-R. Yu, J.-E. Park, Y. Gao, J. K. Bang, M. Zhou, T. D. Veenstra, B. Yeon Kim, K. S. Lee et al.
EMBO J. 31, 3104-3117 (18 July 2012)

Involvement of Polo-like Kinase 1 (Plk1) in Mitotic Arrest by Inhibition of Mitogen-activated Protein Kinase-Extracellular Signal-regulated Kinase-Ribosomal S6 Kinase 1 (MEK-ERK-RSK1) Cascade
R. Li, D.-F. Chen, R. Zhou, S.-N. Jia, J.-S. Yang, J. S. Clegg, and W.-J. Yang
J Biol Chem 287, 15923-15934 (4 May 2012)

Overexpression of Aurora-A Enhances Invasion and Matrix Metalloproteinase-2 Expression in Esophageal Squamous Cell Carcinoma Cells
X. Wang, N. Lu, B. Niu, X. Chen, J. Xie, and N. Cheng
Mol Cancer Res 10, 588-596 (1 May 2012)

Breaking the ties that bind: New advances in centrosome biology
B. R. Mardin, and E. Schiebel
JCB 197, 11-18 (2 April 2012)

Nucleophosmin/B23 activates Aurora A at the centrosome through phosphorylation of serine 89
D. Reboutier, M.-B. Troadec, J.-Y. Cremet, K. Fukasawa, and C. Prigent
JCB 197, 19-26 (2 April 2012)

Structure-function relationship of the Polo-like kinase in Trypanosoma brucei
Z. Yu, Y. Liu, and Z. Li
J. Cell Sci. 125, 1519-1530 (15 March 2012)

G Protein-coupled Receptor Kinase 5 Is Localized to Centrosomes and Regulates Cell Cycle Progression
A. M. Michal, C. H. So, N. Beeharry, H. Shankar, R. Mashayekhi, T. J. Yen, and J. L. Benovic
J Biol Chem 287, 6928-6940 (24 February 2012)

The CUL3-KLHL18 ligase regulates mitotic entry and ubiquitylates Aurora-A
S. Moghe, F. Jiang, Y. Miura, R. L. Cerny, M.-Y. Tsai, and M. Furukawa
Biology Open 1, 82-91 (15 February 2012)

The Renaissance or the cuckoo clock
J. Pines, and I. Hagan
Phil Trans R Soc B 366, 3625-3634 (27 December 2011)

Aurora A and Aurora B jointly coordinate chromosome segregation and anaphase microtubule dynamics
N. Hegarat, E. Smith, G. Nayak, S. Takeda, P. A. Eyers, and H. Hochegger
JCB 195, 1103-1113 (26 December 2011)

Cooperative Phosphorylation of FADD by Aur-A and Plk1 in Response to Taxol Triggers Both Apoptotic and Necrotic Cell Death
M.-S. Jang, S.-J. Lee, N. S. Kang, and E. Kim
Cancer Res. 71, 7207-7215 (1 December 2011)

Arabidopsis {alpha} Aurora Kinases Function in Formative Cell Division Plane Orientation
D. Van Damme, B. De Rybel, G. Gudesblat, D. Demidov, W. Grunewald, I. De Smet, A. Houben, T. Beeckman, and E. Russinova
Plant Cell 23, 4013-4024 (1 November 2011)

Aurora promotes cell division during recovery from TOR-mediated cell cycle arrest by driving spindle pole body recruitment of Polo
L. Halova, and J. Petersen
J. Cell Sci. 124, 3441-3449 (15 October 2011)

The Auto-ubiquitylation of E3 Ubiquitin-protein Ligase Chfr at G2 Phase Is Required for Accumulation of Polo-like Kinase 1 and Mitotic Entry in Mammalian Cells
J.-S. Kim, Y.-Y. Park, S.-Y. Park, H. Cho, D. Kang, and H. Cho
J Biol Chem 286, 30615-30623 (2 September 2011)

Greatwall and Polo-like Kinase 1 Coordinate to Promote Checkpoint Recovery
A. Peng, L. Wang, and L. A. Fisher
J Biol Chem 286, 28996-29004 (19 August 2011)

A genetic screen identifies BRCA2 and PALB2 as key regulators of G2 checkpoint maintenance
T. Menzel, V. Nahse-Kumpf, A. N. Kousholt, D. K. Klein, C. Lund-Andersen, M. Lees, J. V. Johansen, R. G. Syljuasen, and C. S. Sorensen
EMBO Rep. 12, 705-712 (1 July 2011)

Spatial Exclusivity Combined with Positive and Negative Selection of Phosphorylation Motifs Is the Basis for Context-Dependent Mitotic Signaling
J. Alexander, D. Lim, B. A. Joughin, B. Hegemann, J. R. A. Hutchins, T. Ehrenberger, F. Ivins, F. Sessa, O. Hudecz, E. A. Nigg et al.
Sci Signal 4, ra42-ra42 (28 June 2011)

Quantitative Phosphoproteomics Identifies Substrates and Functional Modules of Aurora and Polo-Like Kinase Activities in Mitotic Cells
A. N. Kettenbach, D. K. Schweppe, B. K. Faherty, D. Pechenick, A. A. Pletnev, and S. A. Gerber
Sci Signal 4, rs5-rs5 (28 June 2011)

Polo-like kinases and DNA damage checkpoint: beyond the traditional mitotic functions
E. M. Bahassi, D. K. Schweppe, B. K. Faherty, D. Pechenick, A. A. Pletnev, and S. A. Gerber
Exp Biol Med (Maywood) 236, 648-657 (1 June 2011)

Aurora A Is a Repressed Effector Target of the Chromatin Remodeling Protein INI1/hSNF5 Required for Rhabdoid Tumor Cell Survival
S. Lee, V. Cimica, N. Ramachandra, D. Zagzag, and G. V. Kalpana
Cancer Res. 71, 3225-3235 (1 May 2011)

How protein kinases co-ordinate mitosis in animal cells
H. T. Ma, and R. Y. C. Poon
Biochem. J. 435, 17-31 (1 April 2011)

Inhibitory Phosphorylation of Cyclin-Dependent Kinase 1 as a Compensatory Mechanism for Mitosis Exit
J. P. H. Chow, R. Y. C. Poon, and H. T. Ma
Mol. Cell. Biol. 31, 1478-1491 (1 April 2011)

Growth and Metastases of Human Lung Cancer Are Inhibited in Mouse Xenografts by a Transition State Analogue of 5'-Methylthioadenosine Phosphorylase
I. Basu, J. Locker, M. B. Cassera, T. J. Belbin, E. F. Merino, X. Dong, I. Hemeon, G. B. Evans, C. Guha, V. L. Schramm et al.
J Biol Chem 286, 4902-4911 (11 February 2011)

The Plk1-dependent Phosphoproteome of the Early Mitotic Spindle
A. Santamaria, B. Wang, S. Elowe, R. Malik, F. Zhang, M. Bauer, A. Schmidt, H. H. W. Sillje, R. Korner, E. A. Nigg et al.
MCP 10, M110.004457-M110.004457 (1 January 2011)

A single starfish Aurora kinase performs the combined functions of Aurora-A and Aurora-B in human cells
Y. Abe, E. Okumura, T. Hosoya, T. Hirota, and T. Kishimoto
J. Cell Sci. 123, 3978-3988 (15 November 2010)

The Mitotic Kinase Aurora-A Induces Mammary Cell Migration and Breast Cancer Metastasis by Activating the Cofilin-F-actin Pathway
L.-h. Wang, J. Xiang, M. Yan, Y. Zhang, Y. Zhao, C.-f. Yue, J. Xu, F.-m. Zheng, J.-n. Chen, Z. Kang et al.
Cancer Res. 70, 9118-9128 (15 November 2010)

Radiation pharmacogenomics: A genome-wide association approach to identify radiation response biomarkers using human lymphoblastoid cell lines
N. Niu, Y. Qin, B. L. Fridley, J. Hou, K. R. Kalari, M. Zhu, T.-Y. Wu, G. D. Jenkins, A. Batzler, L. Wang et al.
Genome Res 20, 1482-1492 (1 November 2010)

Golgi Partitioning Controls Mitotic Entry through Aurora-A Kinase
A. Persico, R. I. Cervigni, M. L. Barretta, D. Corda, and A. Colanzi
Mol. Biol. Cell 21, 3708-3721 (1 November 2010)

Phosphorylation and Activation of Androgen Receptor by Aurora-A
S.-K. Shu, Q. Liu, D. Coppola, and J. Q. Cheng
J Biol Chem 285, 33045-33053 (22 October 2010)

The Aurora kinase inhibitor ZM447439 accelerates first meiosis in mouse oocytes by overriding the spindle assembly checkpoint
S. I. R. Lane, H.-Y. Chang, P. C. Jennings, and K. T. Jones
Reproduction 140, 521-530 (1 October 2010)

SPAT-1/Bora acts with Polo-like kinase 1 to regulate PAR polarity and cell cycle progression
A. Noatynska, C. Panbianco, and M. Gotta
Development 137, 3315-3325 (1 October 2010)

Plk1 Regulates Both ASAP Localization and Its Role in Spindle Pole Integrity
G. Eot-Houllier, M. Venoux, S. Vidal-Eychenie, M.-T. Hoang, D. Giorgi, and S. Rouquier
J Biol Chem 285, 29556-29568 (17 September 2010)

Prophase I arrest and progression to metaphase I in mouse oocytes: comparison of resumption of meiosis and recovery from G2-arrest in somatic cells
P. Solc, R. M. Schultz, and J. Motlik
Mol Hum Reprod 16, 654-664 (1 September 2010)

Aurora-A expressing tumour cells are deficient for homology-directed DNA double strand-break repair and sensitive to PARP inhibition
T. Sourisseau, D. Maniotis, A. McCarthy, C. Tang, C. J. Lord, A. Ashworth, and S. Linardopoulos
EMBO Mol Med. 2, 130-142 (1 April 2010)

A Cancer-associated Aurora A Mutant Is Mislocalized and Misregulated Due to Loss of Interaction with TPX2
R. A. Bibby, C. Tang, A. Faisal, K. Drosopoulos, S. Lubbe, R. Houlston, R. Bayliss, and S. Linardopoulos
J Biol Chem 284, 33177-33184 (27 November 2009)

A Genetic Variant of Aurora Kinase A Promotes Genomic Instability Leading to Highly Malignant Skin Tumors
E. C. Torchia, Y. Chen, H. Sheng, H. Katayama, J. Fitzpatrick, W. R. Brinkley, C. Caulin, S. Sen, and D. R. Roop
Cancer Res. 69, 7207-7215 (15 September 2009)

Coupling the cell cycle to development
Y. Budirahardja, and P. Gonczy
Development 136, 2861-2872 (1 September 2009)

Polo-like kinases mediate cell survival in mitochondrial dysfunction
T. Matsumoto, P.-y. Wang, W. Ma, H. J. Sung, S. Matoba, and P. M. Hwang
Proc. Natl. Acad. Sci. USA 106, 14542-14546 (25 August 2009)

FAM29A, a target of Plk1 regulation, controls the partitioning of NEDD1 between the mitotic spindle and the centrosomes
H. Zhu, K. Fang, and G. Fang
J. Cell Sci. 122, 2750-2759 (1 August 2009)

Discovery and Exploitation of Inhibitor-resistant Aurora and Polo Kinase Mutants for the Analysis of Mitotic Networks
P. J. Scutt, M. L. H. Chu, D. A. Sloane, M. Cherry, C. R. Bignell, D. H. Williams, and P. A. Eyers
J Biol Chem 284, 15880-15893 (5 June 2009)

Kinase Signaling in the Spindle Checkpoint
J. Kang, and H. Yu
J Biol Chem 284, 15359-15363 (5 June 2009)

Aurora-A and hBora Join the Game of Polo
L. Macurek, A. Lindqvist, and R. H. Medema
Cancer Res. 69, 4555-4558 (1 June 2009)

Functional Dynamics of Polo-Like Kinase 1 at the Centrosome
K. Kishi, M. A. T. M. van Vugt, K.-i. Okamoto, Y. Hayashi, and M. B. Yaffe
Mol. Cell. Biol. 29, 3134-3150 (1 June 2009)

Plk1 and Aurora A regulate the depolymerase activity and the cellular localization of Kif2a
C.-Y. Jang, J. A. Coppinger, A. Seki, J. R. Yates, and G. Fang
J. Cell Sci. 122, 1334-1341 (1 May 2009)

The decision to enter mitosis: feedback and redundancy in the mitotic entry network
A. Lindqvist, V. Rodriguez-Bravo, and R. H. Medema
JCB 185, 193-202 (20 April 2009)

Aurora-A Kinase Is Essential for Bipolar Spindle Formation and Early Development
D. O. Cowley, J. A. Rivera-Perez, M. Schliekelman, Y. J. He, T. G. Oliver, L. Lu, R. O''Quinn, E. D. Salmon, T. Magnuson, T. Van Dyke et al.
Mol. Cell. Biol. 29, 1059-1071 (15 February 2009)

FAM29A promotes microtubule amplification via recruitment of the NEDD1-{gamma}-tubulin complex to the mitotic spindle
H. Zhu, J. A. Coppinger, C.-Y. Jang, J. R. Yates, and G. Fang
JCB 183, 835-848 (1 December 2008)

Sequestration of Polo kinase to microtubules by phosphopriming-independent binding to Map205 is relieved by phosphorylation at a CDK site in mitosis
V. Archambault, P. P. D''Avino, M. J. Deery, K. S. Lilley, and D. M. Glover
Genes Dev. 22, 2707-2720 (1 October 2008)

Science Signaling. ISSN 1937-9145 (online), 1945-0877 (print). Pre-2008: Science's STKE. ISSN 1525-8882