Abstract
Human Aurora2 was originally identified by its close homology to yeast IPL1 and fly aurora, which are key regulators of chromosome segregation and a family of serine/threonine kinases. Here we demonstrate that the Aurora2 protein is degraded rapidly after G2/M phase release in mammalian cells. Aurora2 protein has a rapid turnover rate with a half-life of approximately 2 h. In eukaryotic cells, the ubiquitin-proteasome pathway is the major mechanism for the targeted degradation of unstable proteins. The treatment of mammalian cells with proteasome inhibitors blocks Aurora2 degradation. Furthermore, Aurora2 is polyubiquitinated in vivo and in vitro using anaphase-promoting complex (APC). These results demonstrate that Aurora2 protein is turned over through the APC-ubiquitin-proteasome pathway.
This is a preview of subscription content, access via your institution
Access options
Subscribe to this journal
Receive 50 print issues and online access
$259.00 per year
only $5.18 per issue
Buy this article
- Purchase on Springer Link
- Instant access to full article PDF
Prices may be subject to local taxes which are calculated during checkout
Similar content being viewed by others
References
Amon A, Irniger S and Nasmyth K . 1994 Cell 77: 1037–1050
Biggins S, Severin FF, Bhalla N, Sassoon I, Hyman AA and Murray AW . 1999 Genes Dev 13: 532–544
Bischoff JR, Anderson L, Zhu Y, Mossie K, Ng L, Souza B, Schryver B, Flanagan P, Clairvoyant F, Ginther C, Chan CS, Novotny M, Slamon DJ and Plowman GD . 1998 EMBO J 17: 3052–3065
Bischoff JR and Plowman GD . 1999 Trends Cell Biol 9: 454–459
Campanero MR and Flemington EK . 1997 Proc Natl Acad Sci USA 94: 2221–2226
Ciechanover A . 1994 Cell 79: 13–21
Ciechanover A . 1998 EMBO J 17: 7151–7160
Fang G, Yu H and Kirschner MW . 1998 Mol Cell 2: 163–171
Fenteany G and Schreiber SL . 1998 J Biol Chem 273: 8545–8548
Francisco L, Wang W and Chan CS . 1994 Mol Cell Biol 14: 4731–4740
Glotzer M, Murray AW and Kirschner MW . 1991 Nature 349: 132–138
Glover DM, Leibowitz MH, McLean DA and Parry H . 1995 Cell 81: 95–105
Gopalan G, Chan CS and Donovan PJ . 1997 J Cell Biol 138: 643–656
Honda R and Yasuda H . 1999 EMBO J 18: 22–27
Kimura M, Kotani S, Hattori T, Sumi N, Yoshioka T, Todokoro K and Okano Y . 1997 J Biol Chem 272: 13766–13771
Koepp DM, Harper JW and Elledge SJ . 1999 Cell 97: 431–434
Maki CG, Huibregtse JM and Howley PM . 1996 Cancer Res 56: 2649–2654
Murray AW, Solomon MJ and Kirschner MW . 1989 Nature 339: 280–286
Pagano M, Tam SW, Theodoras AM, Beer-Romero P, Del Sal G, Chau V, Yew PR, Draetta GF and Rolfe M . 1995 Science 269: 682–685
Rock KL, Gramm C, Rothstein L, Clark K, Stein R, Dick L, Hwang D and Goldberg AL . 1994 Cell 78: 761–771
Salghetti SE, Kim SY and Tansey WP . 1999 EMBO J 18: 717–726
Shindo M, Nakano H, Kuroyanagi H, Shirasawa T, Mihara M, Gilbert DJ, Jenkins NA, Copeland NG, Yagita H and Okumura K . 1998 Biochem Biophys Res Commun 244: 285–292
Stewart E, Kobayashi H, Harrison D and Hunt T . 1994 EMBO J 13: 584–594
Townsley FM, Aristarkhov A, Beck S, Hershko A and Ruderman JV . 1997 Proc Natl Acad Sci USA 94: 2362–2367
Treier M, Staszewski LM and Bohmann D . 1994 Cell 78: 787–798
Urano T, Emkey R and Feig LA . 1996 EMBO J 15: 810–816
Urano T, Furukawa K and Shiku H . 1993 Oncogene 8: 1371–1376
Varshavsky A . 1997 Trends Biochem Sci 22: 383–387
Yanai A, Arama E, Kilfin G and Motro B . 1997 Oncogene 14: 2493–2950
Zhou H, Kuang J, Zhong L, Kuo WL, Gray JW, Sahin A, Brinkley BR and Sen S . 1998 Nat Genet 20: 189–193
Acknowledgements
We thank Drs Dirk Bohmann (European Molecular Biology Laboratory, Heidelberg, Germany) for the histidine-tagged ubiquitin expression vector (pMT107) and Larry A Feig (Tufts University, Boston, MA, USA) for anti-glu monoclonal and anti-Ras polyclonal antibodies. This work was supported by grant-in-aids for Scientific Research and Core of Excellence from the Ministry of Education, Science, Sports and Culture of Japan, and Aichi Cancer research foundation.
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Honda, K., Mihara, H., Kato, Y. et al. Degradation of human Aurora2 protein kinase by the anaphase-promoting complex-ubiquitin-proteasome pathway. Oncogene 19, 2812–2819 (2000). https://doi.org/10.1038/sj.onc.1203609
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1038/sj.onc.1203609
Keywords
This article is cited by
-
Selective targeting of non-centrosomal AURKA functions through use of a targeted protein degradation tool
Communications Biology (2021)
-
A FRET biosensor reveals spatiotemporal activation and functions of aurora kinase A in living cells
Nature Communications (2016)
-
The aurora kinases in cell cycle and leukemia
Oncogene (2015)
-
Benzo[e]pyrimido[5,4-b][1,4]diazepin-6(11H)-one derivatives as Aurora A kinase inhibitors: LQTA-QSAR analysis and detailed systematic validation of the developed model
Molecular Diversity (2015)
-
Anti-centrosome antibodies in breast cancer are the expression of autoimmunity
Immunologic Research (2014)