ArticleMolecular and cellular biology1997
Ras activity late in G1 phase required for p27kip1 downregulation, passage through the restriction point, and entry into S phase in growth factor-stimulated NIH 3T3 fibroblasts.
Article in Molecular and cellular biology, 1997. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 49 papers.
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Who cites it
49 citing papers in PubMed, 167 citations in OpenAlex.
- Review
- Ras signals principally via Erk in G1 but cooperates with PI3K/Akt for Cyclin D induction and S-phase entry.Cell cycle (Georgetown, Tex.) · 2019Article
- Article
- Regulation of hepatitis C virus replication and gene expression by the MAPK-ERK pathway.Virologica Sinica · 2012Article
- Prevention of bronchial hyperplasia by EGFR pathway inhibitors in an organotypic culture model.Cancer prevention research (Philadelphia, Pa.) · 2011Article
- Reviewing once more the c-myc and Ras collaboration: converging at the cyclin D1-CDK4 complex and challenging basic concepts of cancer biology.Cell cycle (Georgetown, Tex.) · 2011Review
- The ERK1/2 mitogen-activated protein kinase pathway as a master regulator of the G1- to S-phase transition.Oncogene · 2007Review
- Focal adhesion kinase controls cellular levels of p27/Kip1 and p21/Cip1 through Skp2-dependent and -independent mechanisms.Molecular and cellular biology · 2006Article
- Activation of PI3K is indispensable for interleukin 7-mediated viability, proliferation, glucose use, and growth of T cell acute lymphoblastic leukemia cells.The Journal of experimental medicine · 2004Article
- p27 deregulation in breast cancer: prognostic significance and implications for therapy.Journal of mammary gland biology and neoplasia · 2004Review
- Deregulation of p27 by oncogenic signaling and its prognostic significance in breast cancer.Breast cancer research : BCR · 2004Review
- p27Kip1 inhibition of GRB2-SOS formation can regulate Ras activation.Molecular and cellular biology · 2003Article
- The cyclopentenone 15-deoxy-delta 12,14-prostaglandin J2 binds to and activates H-Ras.Proceedings of the National Academy of Sciences of the United States of America · 2003Article
- Expression of the cyclin-dependent kinase inhibitor p27 in transitional cell bladder cancers: is it a good predictor for tumor behavior?International urology and nephrology · 2003Article
- Loss of the cell cycle inhibitors p21(Cip1) and p27(Kip1) enhances tumorigenesis in knockout mouse models.Oncogene · 2002Article
- Contrasting effects of basic fibroblast growth factor and neurotrophin 3 on cell cycle kinetics of mouse cortical stem cells.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2002Article
- Cell attachment to the extracellular matrix induces proteasomal degradation of p21(CIP1) via Cdc42/Rac1 signaling.Molecular and cellular biology · 2002Article
- Altered p27(Kip1) phosphorylation, localization, and function in human epithelial cells resistant to transforming growth factor beta-mediated G(1) arrest.Molecular and cellular biology · 2002Article
- Cdk pathway: cyclin-dependent kinases and cyclin-dependent kinase inhibitors.Molecular biotechnology · 2001Article
- Dna damage-induced G(1) arrest in hematopoietic cells is overridden following phosphatidylinositol 3-kinase-dependent activation of cyclin-dependent kinase 2.Molecular and cellular biology · 2001Article
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
It is well documented that Ras functions as a molecular switch for reentry into the cell cycle at the border between G0 and G1 by transducing extracellular growth stimuli into early G1 mitogenic signals. In the present study, we investigated the role of Ras during the late stage of the G1 phase by using NIH 3T3 (M17) fibroblasts in which the expression of a dominant negative Ras mutant, p21(Ha-Ras[Asn17]), is induced in response to dexamethasone treatment. We found that delaying the expression of Ras(Asn17) until late in the G1 phase by introducing dexamethasone 3 h after the addition of epidermal growth factor (EGF) abolished the downregulation of the p27kip1 cyclin-dependent kinase (CDK) inhibitor which normally occurred during this period, with resultant suppression of cyclin Ds/CDK4 and cyclin E/CDK2 and G1 arrest. The immunodepletion of p27kip1 completely eliminated the CDK inhibitor activity from EGF-stimulated, dexamethasone-treated cell lysate. The failure of p27kip1 downregulation and G1 arrest was also observed in cells in which Ras(Asn17) was induced after growth stimulation with a phorbol ester or alpha-thrombin and was mimicked by the addition late in the G1 phase of inhibitors for phosphatidylinositol-3-kinase. Ras-mediated downregulation of p27kip1 involved both the suppression of synthesis and the stimulation of the degradation of the protein. Unlike the earlier expression of Ras(Asn17) at the border between G0 and G1, its delayed expression did not compromise the EGF-stimulated transient activation of extracellular signal-regulated kinases or inhibit the stimulated expression of a principal D-type cyclin, cyclin D1, until close to the border between G1 and S. We conclude that Ras plays temporally distinct, phase-specific roles throughout the G1 phase and that Ras function late in G1 is required for p27kip1 downregulation and passage through the restriction point, a prerequisite for entry into the S phase.
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