p27Kip1 and Cyclin Dependent Kinase 2 Regulate Passage Through the Restriction Point
| Autor: | Jonathan Fretthold, Masahiro Hitomi, Jyoti A. Harwalkar, Ke Yang, Dennis W. Stacey, Yang Guo |
|---|---|
| Rok vydání: | 2006 |
| Předmět: |
DNA Replication
Cell signaling 3T3 cells Mice Cyclin-dependent kinase medicine Animals Phosphorylation Molecular Biology DNA synthesis biology Cell Cycle Cyclin-Dependent Kinase 2 Cyclin-dependent kinase 2 G1 Phase G1/S transition 3T3 Cells Cell Biology Cell cycle Molecular biology Cell biology medicine.anatomical_structure biology.protein Mitogens Restriction point Cyclin-Dependent Kinase Inhibitor p27 Developmental Biology |
| Zdroj: | Cell Cycle. 5:2281-2289 |
| ISSN: | 1551-4005 1538-4101 |
| DOI: | 10.4161/cc.5.19.3318 |
| Popis: | When quiescent cells are stimulated to reenter the cell cycle, growth factors are required only until the restriction point in G(1) phase. After this point the cell no longer requires growth factors, proliferative signaling molecules, or even protein synthesis in order to initiate DNA synthesis, which starts several hours later. Consequently, understanding the molecular nature of the restriction point constitutes one of the major goals in studies of growth regulation. We recently demonstrated that p27Kip1 (p27) regulates passage through G(1) phase in actively proliferating cultures, and initiated these studies to determine if it is also involved in passage through the restriction point following stimulation of quiescent cells. In support of this suggestion, we found that passage through the restriction point requires mitogen-dependent suppression of the high p27 levels normally present in quiescent cells. Moreover, as the culture progresses to mid-G(1) phase, the proportion of cells that pass the restriction point is increased by artificial suppression of p27 levels, while this proportion is reduced by elevation of p27 levels. p27 performs this critical function by regulating the subsequent activating phosphorylation of cyclin dependent kinase (CDK)2, which we also show is necessary for and closely associated with the initiation of DNA synthesis. We conclude that the p27 expression level at mid-G(1) phase determines when a cell passes through the restriction point, and does so by regulating subsequent CDK2 activation. |
| Databáze: | OpenAIRE |
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