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Science 6 December 1996: Vol. 274. no. 5293, pp. 1652 - 1659 DOI: 10.1126/science.274.5293.1652
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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.
Read the Full Text
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Genes & Dev.
17, 101-114
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- Mutational Analysis Reveals a Role for the C Terminus of the Proteasome Subunit Rpt4p in Spindle Pole Body Duplication in Saccharomyces cerevisiae.
- H. B. McDonald, A. H. Helfant, E. M. Mahony, S. K. Khosla, and L. Goetsch (2002)
Genetics
162, 705-720
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- Geminin Deficiency Causes a Chk1-dependent G2 Arrest in Xenopus.
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Mol. Biol. Cell
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- Mad2 and BubR1 Function in a Single Checkpoint Pathway that Responds to a Loss of Tension.
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Mol. Biol. Cell
13, 3706-3719
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- Proteasome Inhibitor PS-341 Inhibits Human Myeloma Cell Growth in Vivo and Prolongs Survival in a Murine Model.
- R. LeBlanc, L. P. Catley, T. Hideshima, S. Lentzsch, C. S. Mitsiades, N. Mitsiades, D. Neuberg, O. Goloubeva, C. S. Pien, J. Adams, et al. (2002)
Cancer Res.
62, 4996-5000
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- Expression of Escherichia coli Methionyl-tRNA Formyltransferase in Saccharomyces cerevisiae Leads to Formylation of the Cytoplasmic Initiator tRNA and Possibly to Initiation of Protein Synthesis with Formylmethionine.
- V. Ramesh, C. Kohrer, and U. L. RajBhandary (2002)
Mol. Cell. Biol.
22, 5434-5442
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- Sgt1p Contributes to Cyclic AMP Pathway Activity and Physically Interacts with the Adenylyl Cyclase Cyr1p/Cdc35p in Budding Yeast.
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Eukaryot. Cell
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- The dynamic localisation of the Drosophila APC/C: evidence for the existence of multiple complexes that perform distinct functions and are differentially localised.
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J. Cell Sci.
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- 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)
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277, 26468-26478
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- Cell Attachment to the Extracellular Matrix Induces Proteasomal Degradation of p21CIP1 via Cdc42/Rac1 Signaling.
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Mol. Cell. Biol.
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- Cell-Cycle Dependent Dynamic Change of 26S Proteasome Distribution in Tobacco BY-2 Cells.
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Plant Cell Physiol.
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- Structural and Functional Analysis of the Human Mitotic-specific Ubiquitin-conjugating Enzyme, UbcH10.
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- Laser Capture Microdissection and Microarray Expression Analysis of Lung Adenocarcinoma Reveals Tobacco Smoking- and Prognosis-related Molecular Profiles.
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Cancer Res.
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- Xic1 degradation in Xenopus egg extracts is coupled to initiation of DNA replication.
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Genes & Dev.
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- Activation of UBC5 Ubiquitin-conjugating Enzyme by the RING Finger of ROC1 and Assembly of Active Ubiquitin Ligases by All Cullins.
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- Chfr Regulates a Mitotic Stress Pathway through its RING-Finger Domain with Ubiquitin Ligase Activity.
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Cancer Res.
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- 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.
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- Multiple Subunits of the Caenorhabditis elegans Anaphase-Promoting Complex Are Required for Chromosome Segregation During Meiosis I.
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Genetics
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- Development of the Proteasome Inhibitor PS-341.
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Oncologist
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- Regulation of the Anaphase-promoting Complex by the Dual Specificity Phosphatase Human Cdc14a.
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- Interaction between Cyclin T1 and SCFSKP2 Targets CDK9 for Ubiquitination and Degradation by the Proteasome.
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