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Science 10 May 1996:
Vol. 272. no. 5263, pp. 877 - 880
DOI: 10.1126/science.272.5263.877
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Reports

Requirement of p27Kip1 for Restriction Point Control of the Fibroblast Cell Cycle

Steve Coats, W. Michael Flanagan, Jamison Nourse, James M. Roberts

Cells deprived of serum mitogens will either undergo immediate cell cycle arrest or complete mitosis and arrest in the next cell cycle. The transition from mitogen dependence to mitogen independence occurs in the mid- to late G1 phase of the cell cycle and is called the restriction point. Murine Balb/c-3T3 fibroblasts deprived of serum mitogens accumulated the cyclin-dependent kinase (CDK) inhibitor p27Kip1. This was correlated with inactivation of essential G1 cyclin-CDK complexes and with cell cycle arrest in G1. The ability of specific mitogens to allow transit through the restriction point paralleled their ability to down-regulate p27, and antisense inhibition of p27 expression prevented cell cycle arrest in response to mitogen depletion. Therefore, p27 is an essential component of the pathway that connects mitogenic signals to the cell cycle at the restriction point.

S. Coats and J. M. Roberts, Department of Basic Sciences, Fred Hutchinson Cancer Research Center, 1124 Columbia Street, Seattle, WA 98104, USA.
W. M. Flanagan, Gilead Sciences, 346 Lakeside Drive, Foster City, CA 94404, USA.
J. Nourse, Program in Cancer Biology, Stanford University Medical School, Stanford, CA 94305, USA.


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   Abstract »    Full Text »    PDF »
Protective Function of p27KIP1 against Apoptosis in Small Cell Lung Cancer Cells in Unfavorable Microenvironments.
A. Masuda, H. Osada, Y. Yatabe, K.-i. Kozaki, Y. Tatematsu, T. Takahashi, T. Hida, T. Takahashi, and T. Takahashi (2001)
Am. J. Pathol. 158, 87-96
   Abstract »    Full Text »    PDF »
Down-Regulation of p27Kip1 Expression Is Required for Development and Function of T Cells.
T. Tsukiyama, N. Ishida, M. Shirane, Y. A. Minamishima, S. Hatakeyama, M. Kitagawa, K. Nakayama, and K.-i. Nakayama (2001)
J. Immunol. 166, 304-312
   Abstract »    Full Text »    PDF »
Rat Protein Tyrosine Phosphatase eta Suppresses the Neoplastic Phenotype of Retrovirally Transformed Thyroid Cells through the Stabilization of p27Kip1.
F. Trapasso, R. Iuliano, A. Boccia, A. Stella, R. Visconti, P. Bruni, G. Baldassarre, M. Santoro, G. Viglietto, and A. Fusco (2000)
Mol. Cell. Biol. 20, 9236-9246
   Abstract »    Full Text »
Analysis of Cyclin D3-cdk4 Complexes in Fibroblasts Expressing and Lacking p27kip1 and p21cip1.
T. K. Bagui, R. J. Jackson, D. Agrawal, and W. J. Pledger (2000)
Mol. Cell. Biol. 20, 8748-8757
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Synergistic Antitumor Effect of Chemotherapy and Antisense-mediated Ablation of the Cell Cycle Inhibitor p27KIP-1.
T. V. Achenbach, R. Müller, and E. P. Slater (2000)
Clin. Cancer Res. 6, 3006-3014
   Abstract »    Full Text »
Down-regulation of p21WAF1/CIP1 or p27Kip1 abrogates antiestrogen-mediated cell cycle arrest in human breast cancer cells.
S. Cariou, J. C. H. Donovan, W. M. Flanagan, A. Milic, N. Bhattacharya, and J. M. Slingerland (2000)
PNAS
   Abstract »    Full Text »
Density-dependent Growth Inhibition of Fibroblasts Ectopically Expressing p27kip1.
X. Zhang, W. Wharton, M. Donovan, D. Coppola, R. Croxton, W. D. Cress, and W. J. Pledger (2000)
Mol. Biol. Cell 11, 2117-2130
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ErbB2 Potentiates Breast Tumor Proliferation through Modulation of p27Kip1-Cdk2 Complex Formation: Receptor Overexpression Does Not Determine Growth Dependency.
H. A. Lane, I. Beuvink, A. B. Motoyama, J. M. Daly, R. M. Neve, and N. E. Hynes (2000)
Mol. Cell. Biol. 20, 3210-3223
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Doxazosin Inhibits Retinoblastoma Protein Phosphorylation and G1->S Transition in Human Coronary Smooth Muscle Cells.
U. Kintscher, S. Wakino, S. Kim, S. M. Jackson, E. Fleck, W. A. Hsueh, and R. E. Law (2000)
Arterioscler Thromb Vasc Biol 20, 1216-1224
   Abstract »    Full Text »    PDF »
Nitric Oxide Modulates Expression of Cell Cycle Regulatory Proteins : A Cytostatic Strategy for Inhibition of Human Vascular Smooth Muscle Cell Proliferation.
F. C. Tanner, P. Meier, H. Greutert, C. Champion, E. G. Nabel, and T. F. Luscher (2000)
Circulation 101, 1982-1989
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v-Jun Overrides the Mitogen Dependence of S-Phase Entry by Deregulating Retinoblastoma Protein Phosphorylation and E2F-Pocket Protein Interactions as a Consequence of Enhanced Cyclin E-cdk2 Catalytic Activity.
W. Clark, E. J. Black, A. MacLaren, U. Kruse, N. LaThangue, P. K. Vogt, and D. A. F. Gillespie (2000)
Mol. Cell. Biol. 20, 2529-2542
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p21Waf1/Cip1 Is an Assembly Factor Required for Platelet-derived Growth Factor-induced Vascular Smooth Muscle Cell Proliferation.
R. H. Weiss, A. Joo, and C. Randour (2000)
J. Biol. Chem. 275, 10285-10290
   Abstract »    Full Text »    PDF »
Reversible G1 Arrest Induced by Inhibition of the Epidermal Growth Factor Receptor Tyrosine Kinase Requires Up-regulation of p27KIP1 Independent of MAPK Activity.
D. Busse, R. S. Doughty, T. T. Ramsey, W. E. Russell, J. O. Price, W. M. Flanagan, L. K. Shawver, and C. L. Arteaga (2000)
J. Biol. Chem. 275, 6987-6995
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Transforming Growth Factor beta 1 Selectively Inhibits the Cyclic AMP-dependent Proliferation of Primary Thyroid Epithelial Cells by Preventing the Association of Cyclin D3-cdk4 with Nuclear p27kip1.
F. Depoortere, I. Pirson, J. Bartek, J. E. Dumont, and P. P. Roger (2000)
Mol. Biol. Cell 11, 1061-1076
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Differential Regulation of P27Kip1 Expression by Mitogenic and Hypertrophic Factors: Involvement of Transcriptional and Posttranscriptional Mechanisms.
M. J. Servant, P. Coulombe, B. Turgeon, and S. Meloche (2000)
J. Cell Biol. 148, 543-556
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Aberrant expression of p27Kip1 is associated with malignant transformation of the rat urinary bladder epithelium.
K. Ogawa, N. Kimoto, M. Asamoto, M. Nakanishi, S. Takahashi, and T. Shirai (2000)
Carcinogenesis 21, 117-121
   Abstract »    Full Text »    PDF »
Expression and modulation of p42/p44 MAPKs and cell cycle regulatory proteins in rat pancreas regeneration.
J. Morisset, J. C. Aliaga, E. L. Calvo, J. Bourassa, and N. Rivard (1999)
Am J Physiol Gastrointest Liver Physiol 277, G953-G959
   Abstract »    Full Text »    PDF »
Low Expression of the Cell Cycle Inhibitor p27Kip1 in Normal Corticotroph Cells, Corticotroph Tumors, and Malignant Pituitary Tumors.
K. Lidhar, M. Korbonits, S. Jordan, Z. Khalimova, G. Kaltsas, X. Lu, R. N. Clayton, P. J. Jenkins, J. P. Monson, G. M. Besser, et al. (1999)
J. Clin. Endocrinol. Metab. 84, 3823-3830
   Abstract »    Full Text »    PDF »
MAP kinase cascade is required for p27 downregulation and S phase entry in fibroblasts and epithelial cells.
N. Rivard, M.-J. Boucher, C. Asselin, and G. L'Allemain (1999)
Am J Physiol Cell Physiol 277, C652-C664
   Abstract »    Full Text »    PDF »
Loss of Cell Cycle Control by Deregulation of Cyclin-dependent Kinase 2 Kinase Activity in Evi-1 Transformed Fibroblasts.
A. Kilbey, V. Stephens, and C. Bartholomew (1999)
Cell Growth Differ. 10, 601-610
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The Cyclins and Cyclin-Dependent Kinase Inhibitors in Hormonal Regulation of Proliferation and Differentiation.
R. G. Pestell, C. Albanese, A. T. Reutens, J. E. Segall, R. J. Lee, and A. Arnold (1999)
Endocr. Rev. 20, 501-534
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Interferon-{{alpha}} Inhibits Proliferation in Human T Lymphocytes by Abrogation of Interleukin 2-induced Changes in Cell Cycle-regulatory Proteins.
S. Erickson, O. Sangfelt, J. Castro, M. Heyman, S. Einhorn, and D. Grandér (1999)
Cell Growth Differ. 10, 575-582
   Abstract »    Full Text »


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