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Science 6 December 1996:
Vol. 274. no. 5293, pp. 1652 - 1659
DOI: 10.1126/science.274.5293.1652

Articles

How Proteolysis Drives the Cell Cycle

Randall W. King, Raymond J. Deshaies, Jan-Michael Peters, * Marc W. Kirschner

Oscillations in the activity of cyclin-dependent kinases (CDKs) promote progression through the eukaryotic cell cycle. This review examines how proteolysis regulates CDK activity--by degrading CDK activators or inhibitors--and also how proteolysis may directly trigger the transition from metaphase to anaphase. Proteolysis during the cell cycle is mediated by two distinct ubiquitin-conjugation pathways. One pathway, requiring CDC34, initiates DNA replication by degrading a CDK inhibitor. The second pathway, involving a large protein complex called the anaphase-promoting complex or cyclosome, initiates chromosome segregation and exit from mitosis by degrading anaphase inhibitors and mitotic cyclins. Proteolysis therefore drives cell cycle progression not only by regulating CDK activity, but by directly influencing chromosome and spindle dynamics.

R. W. King, J.-M. Peters, and M. W. Kirschner are in the Department of Cell Biology, Harvard Medical School, 240 Longwood Ave., Boston, MA 02115, USA. R. J. Deshaies is in the Division of Biology 156-29 California Institute of Technology, Pasadena, CA 91125, USA.
*   Present address: Research Institute for Molecular Pathology, Dr. Bohr-Gasse #7, A-1030 Vienna, Austria.


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Sgt1p Contributes to Cyclic AMP Pathway Activity and Physically Interacts with the Adenylyl Cyclase Cyr1p/Cdc35p in Budding Yeast.
C. Dubacq, R. Guerois, R. Courbeyrette, K. Kitagawa, and C. Mann (2002)
Eukaryot. Cell 1, 568-582
   Abstract »    Full Text »    PDF »
The dynamic localisation of the Drosophila APC/C: evidence for the existence of multiple complexes that perform distinct functions and are differentially localised.
J.-y. Huang and J. W. Raff (2002)
J. Cell Sci. 115, 2847-2856
   Abstract »    Full Text »    PDF »
EDD, the Human Hyperplastic Discs Protein, Has a Role in Progesterone Receptor Coactivation and Potential Involvement in DNA Damage Response.
M. J. Henderson, A. J. Russell, S. Hird, M. Munoz, J. L. Clancy, G. M. Lehrbach, S. T. Calanni, D. A. Jans, R. L. Sutherland, and C. K. W. Watts (2002)
J. Biol. Chem. 277, 26468-26478
   Abstract »    Full Text »    PDF »
Cell Attachment to the Extracellular Matrix Induces Proteasomal Degradation of p21CIP1 via Cdc42/Rac1 Signaling.
W. Bao, M. Thullberg, H. Zhang, A. Onischenko, and S. Stromblad (2002)
Mol. Cell. Biol. 22, 4587-4597
   Abstract »    Full Text »    PDF »
Cell-Cycle Dependent Dynamic Change of 26S Proteasome Distribution in Tobacco BY-2 Cells.
Y. Yanagawa, S. Hasezawa, F. Kumagai, M. Oka, M. Fujimuro, T. Naito, T. Makino, H. Yokosawa, K. Tanaka, A. Komamine, et al. (2002)
Plant Cell Physiol. 43, 604-613
   Abstract »    Full Text »    PDF »
Structural and Functional Analysis of the Human Mitotic-specific Ubiquitin-conjugating Enzyme, UbcH10.
Y. Lin, W. C. Hwang, and R. Basavappa (2002)
J. Biol. Chem. 277, 21913-21921
   Abstract »    Full Text »    PDF »
Laser Capture Microdissection and Microarray Expression Analysis of Lung Adenocarcinoma Reveals Tobacco Smoking- and Prognosis-related Molecular Profiles.
K. Miura, E. D. Bowman, R. Simon, A. C. Peng, A. I. Robles, R. T. Jones, T. Katagiri, P. He, H. Mizukami, L. Charboneau, et al. (2002)
Cancer Res. 62, 3244-3250
   Abstract »    Full Text »    PDF »
Xic1 degradation in Xenopus egg extracts is coupled to initiation of DNA replication.
Z. You, K. Harvey, L. Kong, and J. Newport (2002)
Genes & Dev. 16, 1182-1194
   Abstract »    Full Text »    PDF »
Activation of UBC5 Ubiquitin-conjugating Enzyme by the RING Finger of ROC1 and Assembly of Active Ubiquitin Ligases by All Cullins.
M. Furukawa, T. Ohta, and Y. Xiong (2002)
J. Biol. Chem. 277, 15758-15765
   Abstract »    Full Text »    PDF »
Chfr Regulates a Mitotic Stress Pathway through its RING-Finger Domain with Ubiquitin Ligase Activity.
P. Chaturvedi, V. Sudakin, M. L. Bobiak, P. W. Fisher, M. R. Mattern, S. A. Jablonski, M. R. Hurle, Y. Zhu, T. J. Yen, and B.-B. S. Zhou (2002)
Cancer Res. 62, 1797-1801
   Abstract »    Full Text »    PDF »
A Critical Role for Pin2/TRF1 in ATM-dependent Regulation. INHIBITION OF Pin2/TRF1 FUNCTION COMPLEMENTS TELOMERE SHORTENING, RADIOSENSITIVITY, AND THE G2/M CHECKPOINT DEFECT OF ATAXIA-TELANGIECTASIA CELLS.
S. Kishi and K. P. Lu (2002)
J. Biol. Chem. 277, 7420-7429
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Multiple Subunits of the Caenorhabditis elegans Anaphase-Promoting Complex Are Required for Chromosome Segregation During Meiosis I.
E. S. Davis, L. Wille, B. A. Chestnut, P. L. Sadler, D. C. Shakes, and A. Golden (2002)
Genetics 160, 805-813
   Abstract »    Full Text »    PDF »
Development of the Proteasome Inhibitor PS-341.
J. Adams (2002)
Oncologist 7, 9-16
   Abstract »    Full Text »    PDF »
Regulation of the Anaphase-promoting Complex by the Dual Specificity Phosphatase Human Cdc14a.
J. Bembenek and H. Yu (2001)
J. Biol. Chem. 276, 48237-48242
   Abstract »    Full Text »    PDF »
Interaction between Cyclin T1 and SCFSKP2 Targets CDK9 for Ubiquitination and Degradation by the Proteasome.
R. E. Kiernan, S. Emiliani, K. Nakayama, A. Castro, J. C. Labbe, T. Lorca, K.-i. Nakayama, and M. Benkirane (2001)
Mol. Cell. Biol. 21, 7956-7970
   Abstract »    Full Text »    PDF »



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