|
|
|
|
|
|
|
|
|||||
| Home Help Feedback Subscriptions Archive Search Table of Contents | |||||
First published online 5 May 2004
doi: 10.1242/jcs.01108
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Research Article |
1 Groupe Cycle Cellulaire – CNRS UMR6061 – IFR97, Génomique Fonctionnelle et Santé, Université de Rennes I, 2 avenue du Pr Léon Bernard, 35043 Rennes, France
2 LBCMCP-CNRS UMR5088-IFR109, Institut d'Exploration Fonctionnelle des Génomes, Université Paul Sabatier, 118 route de Narbonne, 31062 Toulouse, France
3 IPBS – CNRS UMR5089, 205 route de Narbonne, 31077 Toulouse, France
* Author for correspondence (e-mail: ducommun{at}cict.fr)
Accepted 19 January 2004
Aurora-A protein kinase, which is the product of an oncogene, is required for the assembly of a functional mitotic apparatus and the regulation of cell ploidy. Overexpression of Aurora-A in tumour cells has been correlated with cancer susceptibility and poor prognosis. Aurora-A activity is required for the recruitment of CDK1-cyclin B1 to the centrosome prior to its activation and the commitment of the cell to mitosis. In this report, we demonstrate that the CDC25B phosphatase, an activator of cyclin dependent kinases at mitosis, is phosphorylated both in vitro and in vivo by Aurora-A on serine 353 and that this phosphorylated form of CDC25B is located at the centrosome during mitosis. Knockdown experiments by RNAi confirm that the centrosome phosphorylation of CDC25B on S353 depends on Aurora-A kinase. Microinjection of antibodies against phosphorylated S353 results in a mitotic delay whilst overexpression of a S353 phosphomimetic mutant enhances the mitotic inducing effect of CDC25B. Our results demonstrate that Aurora-A phosphorylates CDC25B in vivo at the centrosome during mitosis. This phosphorylation might locally participate in the control of the onset of mitosis. These findings re-emphasise the role of the centrosome as a functional integrator of the pathways contributing to the triggering of mitosis.
Key words: Aurora-A, CDC25B phosphatase, Centrosome, Mitosis
This article has been cited by other articles:
|
|
 |
|
  L.-Y. Lu, J. L. Wood, L. Ye, K. Minter-Dykhouse, T. L. Saunders, X. Yu, and J. Chen Aurora A Is Essential for Early Embryonic Development and Tumor Suppression J. Biol. Chem., November 14, 2008; 283(46): 31785 - 31790. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. Boutros, V. Lobjois, and B. Ducommun CDC25B Involvement in the Centrosome Duplication Cycle and in Microtubule Nucleation Cancer Res., December 15, 2007; 67(24): 11557 - 11564. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. R. Barr and F. Gergely Aurora-A: the maker and breaker of spindle poles J. Cell Sci., September 1, 2007; 120(17): 2987 - 2996. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Feng, A. Yu, Y. Liu, J. Zhang, Z. Zong, W. Su, Z. Zhang, D. Yu, Q.-Y. Sun, and B. Yu Involvement of Protein Kinase B/AKT in Early Development of Mouse Fertilized Eggs Biol Reprod, September 1, 2007; 77(3): 560 - 568. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Cha, X. Wang, H. Li, and A. J. Fornace Jr. A Functional Role for p38 MAPK in Modulating Mitotic Transit in the Absence of Stress J. Biol. Chem., August 3, 2007; 282(31): 22984 - 22992. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. Bansal and J. S. Lazo Induction of Cdc25B Regulates Cell Cycle Resumption after Genotoxic Stress Cancer Res., April 1, 2007; 67(7): 3356 - 3363. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. T. Keady, P. Kuo, S. E. Martinez, L. Yuan, and L. E. Hake MAPK interacts with XGef and is required for CPEB activation during meiosis in Xenopus oocytes J. Cell Sci., March 15, 2007; 120(6): 1093 - 1103. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. Tanaka, Y. Hashimoto, T. Ito, K. Kondo, M. Higashiyama, S. Tsunoda, C. Ortiz, Y. Sakai, J. Inazawa, and Y. Shimada The Suppression of Aurora-A/STK15/BTAK Expression Enhances Chemosensitivity to Docetaxel in Human Esophageal Squamous Cell Carcinoma Clin. Cancer Res., February 15, 2007; 13(4): 1331 - 1340. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Cazales, R. Boutros, M.-C. Brezak, S. Chaumeron, G. Prevost, and B. Ducommun Pharmacologic inhibition of CDC25 phosphatases impairs interphase microtubule dynamics and mitotic spindle assembly Mol. Cancer Ther., January 1, 2007; 6(1): 318 - 325. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. D. Carvajal, A. Tse, and G. K. Schwartz Aurora Kinases: New Targets for Cancer Therapy Clin. Cancer Res., December 1, 2006; 12(23): 6869 - 6875. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. Schmitt, R. Boutros, C. Froment, B. Monsarrat, B. Ducommun, and C. Dozier CHK1 phosphorylates CDC25B during the cell cycle in the absence of DNA damage J. Cell Sci., October 15, 2006; 119(20): 4269 - 4275. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Q. Liu and J. V. Ruderman Aurora A, mitotic entry, and spindle bipolarity PNAS, April 11, 2006; 103(15): 5811 - 5816. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Lindqvist, H. Kallstrom, A. Lundgren, E. Barsoum, and C. K. Rosenthal Cdc25B cooperates with Cdc25A to induce mitosis but has a unique role in activating cyclin B1-Cdk1 at the centrosome J. Cell Biol., October 10, 2005; 171(1): 35 - 45. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M.-C. Brezak, M. Quaranta, M.-O. Contour-Galcera, O. Lavergne, O. Mondesert, P. Auvray, P. G. Kasprzyk, G. P. Prevost, and B. Ducommun Inhibition of human tumor cell growth in vivo by an orally bioavailable inhibitor of CDC25 phosphatases Mol. Cancer Ther., September 1, 2005; 4(9): 1378 - 1387. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C.-T. R. Yu, J.-M. Hsu, Y.-C. G. Lee, A.-P. Tsou, C.-K. Chou, and C.-Y. F. Huang Phosphorylation and Stabilization of HURP by Aurora-A: Implication of HURP as a Transforming Target of Aurora-A Mol. Cell. Biol., July 15, 2005; 25(14): 5789 - 5800. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. R. Wonsey and M. T. Follettie Loss of the Forkhead Transcription Factor FoxM1 Causes Centrosome Amplification and Mitotic Catastrophe Cancer Res., June 15, 2005; 65(12): 5181 - 5189. [Abstract] [Full Text] [PDF]
|
|
