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Science 26 March 1993:
Vol. 259. no. 5103, pp. 1908 - 1912
DOI: 10.1126/science.8384376

Articles

Science, Vol 259, Issue 5103, 1908-1912
Copyright © 1993 by American Association for the Advancement of Science


articles

Cyclin-dependent regulation of G1 in mammalian fibroblasts

M Ohtsubo and JM Roberts

Department of Basic Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA 98104.

Eukaryotic cells become committed to proliferate during the G1 phase of the cell cycle. In budding yeast, commitment occurs when the catalytic subunit of a protein kinase, encoded by the CDC28 gene (the homolog of the fission yeast cdc2+ gene), binds to a positively acting regulatory subunit, a cyclin. Related kinases are also required for progression through the G1 phase in higher eukaryotes. The role of cyclins in controlling G1 progression in mammalian cells was tested by construction of fibroblasts that constitutively overexpress human cyclin E. This was found to shorten the duration of G1, decrease cell size, and diminish the serum requirement for the transition from G1 to S phase. These observations show that cyclin levels can be rate-limiting for G1 progression in mammalian cells and suggest that cyclin synthesis may be the target of physiological signals that control cell proliferation.


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FASEB J 12, 1233-1239
   Abstract »    Full Text »
Active Cyclin A-CDK2 Complex, a Possible Critical Factor for Cell Proliferation in Human Primary Lung Carcinomas.
Y. Dobashi, M. Shoji, S.-X. Jiang, M. Kobayashi, Y. Kawakubo, and T. Kameya (1998)
Am. J. Pathol. 153, 963-972
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Neuronal Damage and Plasticity Identified by Microtubule-Associated Protein 2, Growth-Associated Protein 43, and Cyclin D1 Immunoreactivity After Focal Cerebral Ischemia in Rats • Editorial Comment.
Y. Li, N. Jiang, C. Powers, M. Chopp, and B. B. Johansson (1998)
Stroke 29, 1972-1981
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The Cyclin E Promoter Is Activated by Human Cytomegalovirus 86-kDa Immediate Early Protein.
W. A. Bresnahan, T. Albrecht, and E. A. Thompson (1998)
J. Biol. Chem. 273, 22075-22082
   Abstract »    Full Text »    PDF »
Multiple G1 Regulatory Elements Control the Androgen-dependent Proliferation of Prostatic Carcinoma Cells.
K. E. Knudsen, K. C. Arden, and W. K. Cavenee (1998)
J. Biol. Chem. 273, 20213-20222
   Abstract »    Full Text »    PDF »
Cyclin E Associates with Components of the Pre-mRNA Splicing Machinery in Mammalian Cells.
W. Seghezzi, K. Chua, F. Shanahan, O. Gozani, R. Reed, and E. Lees (1998)
Mol. Cell. Biol. 18, 4526-4536
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Transcription Factor E2F and Cyclin E-Cdk2 Complex Cooperate to Induce Chromosomal DNA Replication in Xenopus Oocytes.
E. Akamatsu, T. Tanaka, and J.-y. Kato (1998)
J. Biol. Chem. 273, 16494-16500
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Increased Expression of Cyclin D2 during Multiple States of Growth Arrest in Primary and Established Cells.
M. Meyyappan, H. Wong, C. Hull, and K. T. Riabowol (1998)
Mol. Cell. Biol. 18, 3163-3172
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Nitric Oxide–Induced Downregulation of Cdk2 Activity and Cyclin A Gene Transcription in Vascular Smooth Muscle Cells.
K. Guo, V. Andres, and K. Walsh (1998)
Circulation 97, 2066-2072
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p21 Is a Critical CDK2 Regulator Essential for Proliferation Control in Rb-deficient Cells.
J. Brugarolas, R. T. Bronson, and T. Jacks (1998)
J. Cell Biol. 141, 503-514
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Identification of a substrate-targeting domain in cyclin E necessary for phosphorylation of the retinoblastoma protein.
B. L. Kelly, K. G. Wolfe, and J. M. Roberts (1998)
PNAS 95, 2535-2540
   Abstract »    Full Text »    PDF »
Expression of NPAT, a novel substrate of cyclin E-CDK2, promotes S-phase entry.
J. Zhao, B. Dynlacht, T. Imai, T.-a. Hori, and E. Harlow (1998)
Genes & Dev. 12, 456-461
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Disruption of the G1/S Transition in Human Papillomavirus Type 16 E7-Expressing Human Cells Is Associated with Altered Regulation of Cyclin E.
L. G. Martin, G. W. Demers, and D. A. Galloway (1998)
J. Virol. 72, 975-985
   Abstract »    Full Text »    PDF »



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