Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.

Site Tools

  • AAAS
  • Subscribe
  • Feedback

Site Search

Search Advanced

Science 29 October 2004:
Vol. 306. no. 5697, pp. 885 - 888
DOI: 10.1126/science.1103544
Prev | Table of Contents | Next

Reports

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 of the cell cycle and promotes polyploidy, which may contribute to genomic instability in cancer cells. We identified 20 amino acids 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 localized on the centrosome, prevented endogenous cyclin E and cyclin A from localizing to the centrosome, and inhibited DNA synthesis. Ectopic cyclin E localized to the centrosome and accelerated S phase entry even with mutations that abolish Cdk2 binding, but not with a mutation in the CLS. These results suggest that cyclin E has a modular centrosomal-targeting domain essential for 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

Read the Full Text


THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
Orc1 Controls Centriole and Centrosome Copy Number in Human Cells.
A. S. Hemerly, S. G. Prasanth, K. Siddiqui, and B. Stillman (2009)
Science 323, 789-793
   Abstract »    Full Text »    PDF »
cAMP-mediated Induction of Cyclin E Sensitizes Growth-arrested Adipose Stem Cells to DNA Damage-induced Apoptosis.
H. Ugland, A. C. Boquest, S. Naderi, P. Collas, and H. K. Blomhoff (2008)
Mol. Biol. Cell 19, 5082-5092
   Abstract »    Full Text »    PDF »
Cyclin E-dependent localization of MCM5 regulates centrosome duplication.
R. L. Ferguson and J. L. Maller (2008)
J. Cell Sci. 121, 3224-3232
   Abstract »    Full Text »    PDF »
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.
T. Shimizu, L.-L. Ho, and Z.-C. Lai (2008)
Genetics 178, 957-965
   Abstract »    Full Text »    PDF »
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
   Full Text »    PDF »
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.
D. Y. Kim and R. Roy (2006)
J. Cell Biol. 174, 751-757
   Abstract »    Full Text »    PDF »
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 »


To Advertise     Find Products

Science. ISSN 0036-8075 (print), 1095-9203 (online)