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Science 24 December 1993: Vol. 262. no. 5142, pp. 2050 - 2054 DOI: 10.1126/science.8266103
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Articles
Science, Vol 262, Issue 5142, 2050-2054
Copyright © 1993 by American Association for the Advancement of Science
Distinct roles for cyclin-dependent kinases in cell cycle control
S van den Heuvel
and
E Harlow
Massachusetts General Hospital Cancer Center, Charlestown 02129.
The key cell-cycle regulator Cdc2 belongs to a family of cyclin-dependent kinases in higher eukaryotes. Dominant-negative mutations were used to address the requirement for kinases of this family in progression through the human cell cycle. A dominant-negative Cdc2 mutant arrested cells at the G2 to M phase transition, whereas mutants of the cyclin-dependent kinases Cdk2 and Cdk3 caused a G1 block. The mutant phenotypes were specifically rescued by the corresponding wild-type kinases. These data reveal that Cdk3, in addition to Cdc2 and Cdk2, executes a distinct and essential function in the mammalian cell cycle.
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- pRb Inactivation in Senescent Cells Leads to an E2F-Dependent Apoptosis Requiring p73.
- K. Alexander, H.-S. Yang, and P. W. Hinds (2003)
Mol. Cancer Res.
1, 716-728
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- Human Spy1 Promotes Survival of Mammalian Cells following DNA Damage.
- E. A. Barnes, L. A. Porter, J.-L. Lenormand, R. W. Dellinger, and D. J. Donoghue (2003)
Cancer Res.
63, 3701-3707
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- Expression of Cyclin-Dependent Kinase 6, but not Cyclin-Dependent Kinase 4, Alters Morphology of Cultured Mouse Astrocytes.
- K. K. Ericson, D. Krull, P. Slomiany, and M. J. Grossel (2003)
Mol. Cancer Res.
1, 654-664
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- {alpha}v{beta}3 integrin expression up-regulates cdc2, which modulates cell migration.
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J. Cell Biol.
161, 817-826
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- Genetic Models in Applied Physiology: Invited Review: Effect of oxygen deprivation on cell cycle activity: a profile of delay and arrest.
- R. M. Douglas and G. G. Haddad (2003)
J Appl Physiol
94, 2068-2083
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- Herpes simplex virus 1 activates cdc2 to recruit topoisomerase IIalpha for post-DNA synthesis expression of late genes.
- S. J. Advani, R. R. Weichselbaum, and B. Roizman (2003)
PNAS
100, 4825-4830
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- Inhibition of Cdk4 Activity Enhances Translation of p27kip1 in Quiescent Rb-negative Cells.
- T. Gonzalez, M. Seoane, P. Caamano, J. Vinuela, F. Dominguez, and J. Zalvide (2003)
J. Biol. Chem.
278, 12688-12695
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- The E2F-Cdc2 Cell-Cycle Pathway Specifically Mediates Activity Deprivation-Induced Apoptosis of Postmitotic Neurons.
- Y. Konishi and A. Bonni (2003)
J. Neurosci.
23, 1649-1658
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- Casein Kinase 2 Interacts with Cyclin-dependent Kinase 11 (CDK11) in Vivo and Phosphorylates Both the RNA Polymerase II Carboxyl-terminal Domain and CDK11 in Vitro.
- J. H. Trembley, D. Hu, C. A. Slaughter, J. M. Lahti, and V. J. Kidd (2003)
J. Biol. Chem.
278, 2265-2270
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- Structure-based Design of p18INK4c Proteins with Increased Thermodynamic Stability and Cell Cycle Inhibitory Activity.
- R. N. Venkataramani, T. K. MacLachlan, X. Chai, W. S. El-Deiry, and R. Marmorstein (2002)
J. Biol. Chem.
277, 48827-48833
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- Effects of Tea on Preneoplastic Lesions and Cell Cycle Regulators in Rat Liver.
- X. Jia, C. Han, and J. Chen (2002)
Cancer Epidemiol. Biomarkers Prev.
11, 1663-1667
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- Cyclin-dependent kinases as cellular targets for antiviral drugs.
- L. M. Schang (2002)
J. Antimicrob. Chemother.
50, 779-792
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- Cell Cycle Inhibition by FoxO Forkhead Transcription Factors Involves Downregulation of Cyclin D.
- M. Schmidt, S. Fernandez de Mattos, A. van der Horst, R. Klompmaker, G. J. P. L Kops, E. W.-F. Lam, B. M. T. Burgering, and R. H. Medema (2002)
Mol. Cell. Biol.
22, 7842-7852
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- Coupling of DNA Synthesis and Histone Synthesis in S Phase Independent of Cyclin/cdk2 Activity.
- D. M. Nelson, X. Ye, C. Hall, H. Santos, T. Ma, G. D. Kao, T. J. Yen, J. W. Harper, and P. D. Adams (2002)
Mol. Cell. Biol.
22, 7459-7472
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- Inhibition of Hypoxia-Induced Apoptosis by Modulation of Retinoblastoma Protein-Dependent Signaling in Cardiomyocytes.
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Circ. Res.
91, 782-789
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- Cyclin-Dependent Kinase-2 Controls Oligodendrocyte Progenitor Cell Cycle Progression and Is Downregulated in Adult Oligodendrocyte Progenitors.
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J. Neurosci.
22, 8553-8562
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- Interaction of the c-Jun/JNK Pathway and Cyclin-dependent Kinases in Death of Embryonic Cortical Neurons Evoked by DNA Damage.
- M. H. Ghahremani, E. Keramaris, T. Shree, Z. Xia, R. J. Davis, R. Flavell, R. S. Slack, and D. S. Park (2002)
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277, 35586-35596
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- Expression of wild type and mutant TSC2, but not TSC1, causes an increase in the G1 fraction of the cell cycle in HEK293 cells.
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J. Med. Genet.
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- Hepatitis B Virus X Protein Activates the p38 Mitogen-Activated Protein Kinase Pathway in Dedifferentiated Hepatocytes.
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J. Virol.
76, 9763-9772
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- The mechanism regulating the dissociation of the centrosomal protein C-Nap1 from mitotic spindle poles.
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J. Cell Sci.
115, 3275-3284
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- Cyclin D-cdk4 activity modulates the subnuclear localization and interaction of MEF2 with SRC-family coactivators during skeletal muscle differentiation.
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Genes & Dev.
16, 1792-1805
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- Flavopiridol and Trastuzumab Synergistically Inhibit Proliferation of Breast Cancer Cells: Association with Selective Cooperative Inhibition of Cyclin D1-dependent Kinase and Akt Signaling Pathways.
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Mol. Cancer Ther.
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- Explant-Induced Reactivation of Herpes Simplex Virus Occurs in Neurons Expressing Nuclear cdk2 and cdk4.
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J. Virol.
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