p27Kip1 and cyclin dependent kinase 2 regulate passage through the restriction point.

p27Kip1 and cyclin dependent kinase 2 regulate passage through the restriction point. Research Abstract Details 

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p27Kip1 and cyclin dependent kinase 2 regulate passage through the restriction point. Abstract Text:

Masahiro Hitomi,Ke Yang,Yang Guo,Jonathan Fretthold,Jyoti Harwalkar,Dennis W Stacey,

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.

p27Kip1 and cyclin dependent kinase 2 regulate passage through the restriction point. Publishing Authors By Initials

M Hitomi,K Yang,Y Guo,J Fretthold,J Harwalkar,DW Stacey,

For similar biochemical phenomena, metabolism, and nutrition: metabolism: phosphorylation research abstracts see: biochemical phenomena, metabolism, and nutrition: metabolism: phosphorylation research

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p27Kip1 and cyclin dependent kinase 2 regulate passage through the restriction point. Journal Published:

PUBLICATION TYPE: Research Support, N.I.H., Extr

Journal: Cell cycle (Georgetown, Tex.)

VOLUME: 5

Page Numbers: 2281-9

Journal Abbreviation: Cell Cycle

ISSN: 1551-4005

DAY: 1

MONTH: 10

YEAR: 2006

p27Kip1 and cyclin dependent kinase 2 regulate passage through the restriction point. Information

Number of References:

LANGUAGE: eng

NlmUniqueID: 101137841

p27Kip1 and cyclin dependent kinase 2 regulate passage through the restriction point. Keywords Mesh Terms:

KEYWORDS: Phosphorylation

MESH TERMS: pharmacology

Chemical & Substance for Abstract: p27Kip1 and cyclin dependent kinase 2 regulate passage through the restriction point. Information

Substance Name: Cyclin-Dependent Kinase 2

Registry Number: EC 2.7.1.37

Grant and Affiliation Information for p27Kip1 and cyclin dependent kinase 2 regulate passage through the restriction point.

AFFILIATION: The Department of Molecular Genetics, The Lerner Research Institute, The Cleveland Clinic Foundation, Cleveland, Ohio 44195, USA. hitomim@ccf.org

Country: United States

AGENCY: United States NIGMS

GRANT: GM52271

ACRONYM: GM

MEDLINETA: Cell Cycle

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