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A Centrosomal Localization Signal in Cyclin E Required for Cdk2-Independent S Phase Entry
Yutaka Matsumoto and
James L. Maller*
Excess cyclin E–Cdk2 accelerates entry into S phase ofthe cell cycle and promotes polyploidy, which may contributeto genomic instability in cancer cells. We identified 20 aminoacids in cyclin E as a centrosomal localization signal (CLS)essential for both centrosomal targeting and promoting DNA synthesis.Expressed wild-type, but not mutant, CLS peptides localizedon the centrosome, prevented endogenous cyclin E and cyclinA from localizing to the centrosome, and inhibited DNA synthesis.Ectopic cyclin E localized to the centrosome and acceleratedS phase entry even with mutations that abolish Cdk2 binding,but not with a mutation in the CLS. These results suggest thatcyclin E has a modular centrosomal-targeting domain essentialfor promoting S phase entry in a Cdk2-independent manner.
Howard Hughes Medical Institute (HHMI) and Department of Pharmacology, University of Colorado School of Medicine, Denver, CO 80262, USA.
* To whom correspondence should be addressed. E-mail: Jim.Maller{at}uchsc.edu
Cyclin E Overexpression in Epithelial Ovarian Cancer Characterizes an Etiologic Subgroup.
J. M. Schildkraut, P. G. Moorman, A. E. Bland, S. Halabi, B. Calingaert, R. Whitaker, P. S. Lee, T. Elkins-Williams, R. C. Bentley, J. R. Marks, et al. (2008)
Cancer Epidemiol. Biomarkers Prev.
17, 585-593
|Abstract »|Full Text »|PDF »
The mob as tumor suppressor Gene Is Essential for Early Development and Regulates Tissue Growth in Drosophila.
Human Papillomavirus Type 16 E7 Oncoprotein Associates with the Centrosomal Component {gamma}-Tubulin.
C. L. Nguyen, C. Eichwald, M. L. Nibert, and K. Munger (2007)
J. Virol.
81, 13533-13543
|Abstract »|Full Text »|PDF »
Loss of p27Kip1 enhances tumor progression in chronic hepatocyte injury-induced liver tumorigenesis with widely ranging effects on Cdk2 or Cdc2 activation.
D. Sun, H. Ren, M. Oertel, R. S. Sellers, and L. Zhu (2007)
Carcinogenesis
28, 1859-1866
|Abstract »|Full Text »|PDF »
Cyclin E Associated Kinase Activity Predicts Response to Platinum-Based Chemotherapy.
I. Bedrosian, C. Lee, S. L. Tucker, S. L. Palla, K. Lu, and K. Keyomarsi (2007)
Clin. Cancer Res.
13, 4800-4806
|Abstract »|Full Text »|PDF »
Structure and duplication of the centrosome.
J. Azimzadeh and M. Bornens (2007)
J. Cell Sci.
120, 2139-2142
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Epstein-Barr Virus Thymidine Kinase Is a Centrosomal Resident Precisely Localized to the Periphery of Centrioles.
M. B. Gill, J. L. Kutok, and J. D. Fingeroth (2007)
J. Virol.
81, 6523-6535
|Abstract »|Full Text »|PDF »
Cyclin e expression and outcome in pancreatic ductal adenocarcinoma..
D. A. Skalicky, J. G. Kench, D. Segara, M. J. Coleman, R. L. Sutherland, S. M. Henshall, E. A. Musgrove, and A. V. Biankin (2006)
Cancer Epidemiol. Biomarkers Prev.
15, 1941-1947
|Abstract »|Full Text »|PDF »
Cell cycle regulators control centrosome elimination during oogenesis in Caenorhabditis elegans.
Inhibition of centrosome protein assembly leads to p53-dependent exit from the cell cycle.
V. Srsen, N. Gnadt, A. Dammermann, and A. Merdes (2006)
J. Cell Biol.
174, 625-630
|Abstract »|Full Text »|PDF »
Fate of centrosomes following somatic cell nuclear transfer (SCNT) in bovine oocytes..
Y. Dai, L. Wang, H. Wang, Y. Liu, N. Li, Q. Lyu, D. L Keefe, D. F Albertini, and L. Liu (2006)
Reproduction
131, 1051-1061
|Abstract »|Full Text »|PDF »
Polo Box Domain of Plk3 Functions as a Centrosome Localization Signal, Overexpression of Which Causes Mitotic Arrest, Cytokinesis Defects, and Apoptosis.
N. Jiang, X. Wang, M. Jhanwar-Uniyal, Z. Darzynkiewicz, and W. Dai (2006)
J. Biol. Chem.
281, 10577-10582
|Abstract »|Full Text »|PDF »
Cell Cycle Defects Contribute to a Block in Hormone-induced Mammary Gland Proliferation in CCAAT/Enhancer-binding Protein (C/EBP{beta})-null Mice.
S. L. Grimm, A. Contreras, M.-H. Barcellos-Hoff, and J. M. Rosen (2005)
J. Biol. Chem.
280, 36301-36309
|Abstract »|Full Text »|PDF »
