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Identification of Cyclin-dependent Kinase 1 Specific Phosphorylation Sites by an In Vitro Kinase Assay
Published on: May 3, 2018
p27Kip1 and cyclin dependent kinase 2 regulate passage through the restriction point
Masahiro Hitomi1, Ke Yang, Yang Guo
1The Department of Molecular Genetics, The Lerner Research Institute, The Cleveland Clinic Foundation, Cleveland, Ohio 44195, USA. hitomim@ccf.org
Cell Cycle (Georgetown, Tex.)
|September 14, 2006
Summary
Cell cycle progression past the restriction point requires the suppression of p27Kip1 (p27). This protein regulates cyclin-dependent kinase 2 (CDK2) activation, controlling entry into DNA synthesis.
Area of Science:
- Cell Biology
- Molecular Biology
- Cell Cycle Regulation
Background:
- Growth factors are essential for cell cycle reentry until the G1 restriction point.
- The molecular mechanisms governing the restriction point remain a key area of research in growth regulation.
Purpose of the Study:
- To investigate the role of p27Kip1 (p27) in the restriction point passage of quiescent cells stimulated to proliferate.
- To determine if p27 regulates entry into DNA synthesis via CDK2 activation.
Main Methods:
- Studied quiescent cell cultures stimulated to reenter the cell cycle.
- Manipulated p27Kip1 levels (suppression and elevation) in mid-G1 phase.
- Assessed cell passage through the restriction point.
- Analyzed cyclin-dependent kinase 2 (CDK2) phosphorylation and its association with DNA synthesis.
Main Results:
- Passage through the restriction point necessitates mitogen-dependent reduction of high p27 levels in quiescent cells.
- Artificial suppression of p27 increased the proportion of cells passing the restriction point.
- Elevated p27 levels reduced the proportion of cells successfully navigating the restriction point.
- p27 regulates the activating phosphorylation of CDK2, which is critical for DNA synthesis initiation.
Conclusions:
- p27Kip1 expression levels at mid-G1 phase are critical determinants of restriction point passage.
- p27 controls cell cycle progression by modulating CDK2 activation, thereby regulating DNA synthesis initiation.
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