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Selective chemical inhibition as a tool to study Cdk1 and Cdk2 functions in the cell cycle.
Krasinska L
,
Cot E
,
Fisher D
.
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Cyclin-dependent kinases are highly conserved among all eukaryotes, and have essential roles in the cell cycle. However, these roles are still only poorly understood at a molecular level, partly due to the functional redundancy of different Cdk complexes. Indeed, mice knockouts have even thrown into some doubt the assumed essential roles for Cdk2-cyclin E in triggering S-phase, but this is almost certainly due to compensation by Cdk1 complexes. By combining both knockout approaches and chemical Cdk inhibition in Xenopus egg extracts, we have shown that one reason for functional redundancy of Cdk control of S-phase is that Cdk activity required to trigger S-phase is very low. Cdk1 contributes to this activity even in the presence of Cdk2, and Cdk activity at this stage does not show "switch-like" regulation, as at the onset of mitosis. It is important to try to confirm and extend these findings to other cell-types, and to explain why different cells might have evolved different requirements for Cdk activity. In this paper, we present data that suggest that selective chemical Cdk inhibition will be a useful tool towards achieving this goal.
Ait-Si-Ali,
Histone acetyltransferase activity of CBP is controlled by cycle-dependent kinases and oncoprotein E1A.
1998, Pubmed
Ait-Si-Ali,
Histone acetyltransferase activity of CBP is controlled by cycle-dependent kinases and oncoprotein E1A.
1998,
Pubmed
Aleem,
Cdc2-cyclin E complexes regulate the G1/S phase transition.
2005,
Pubmed
Bain,
The selectivity of protein kinase inhibitors: a further update.
2007,
Pubmed
Baus,
Permanent cell cycle exit in G2 phase after DNA damage in normal human fibroblasts.
2003,
Pubmed
Berthet,
Cdk2 knockout mice are viable.
2003,
Pubmed
Burgess,
Inhibition of S/G2 phase CDK4 reduces mitotic fidelity.
2006,
Pubmed
D'Angiolella,
Role for cyclin-dependent kinase 2 in mitosis exit.
2001,
Pubmed
,
Xenbase
Davies,
Structure-based design of a potent purine-based cyclin-dependent kinase inhibitor.
2002,
Pubmed
Donaldson,
CLB5-dependent activation of late replication origins in S. cerevisiae.
1998,
Pubmed
Du,
Critical role of CDK2 for melanoma growth linked to its melanocyte-specific transcriptional regulation by MITF.
2004,
Pubmed
Fang,
Evidence that the G1-S and G2-M transitions are controlled by different cdc2 proteins in higher eukaryotes.
1991,
Pubmed
,
Xenbase
Fisher,
A single fission yeast mitotic cyclin B p34cdc2 kinase promotes both S-phase and mitosis in the absence of G1 cyclins.
1996,
Pubmed
Gabrielli,
A cdc2-related kinase oscillates in the cell cycle independently of cyclins G2/M and cdc2.
1992,
Pubmed
,
Xenbase
Hagan,
Cloning and sequencing of the cyclin-related cdc13+ gene and a cytological study of its role in fission yeast mitosis.
1988,
Pubmed
Hochegger,
An essential role for Cdk1 in S phase control is revealed via chemical genetics in vertebrate cells.
2007,
Pubmed
Knoblich,
Cyclin E controls S phase progression and its down-regulation during Drosophila embryogenesis is required for the arrest of cell proliferation.
1994,
Pubmed
Krasinska,
Cdk1 and Cdk2 activity levels determine the efficiency of replication origin firing in Xenopus.
2008,
Pubmed
,
Xenbase
Krasinska,
Regulation of multiple cell cycle events by Cdc14 homologues in vertebrates.
2007,
Pubmed
,
Xenbase
Labbé,
MPF from starfish oocytes at first meiotic metaphase is a heterodimer containing one molecule of cdc2 and one molecule of cyclin B.
1989,
Pubmed
Lemaitre,
Mitotic remodeling of the replicon and chromosome structure.
2005,
Pubmed
,
Xenbase
Lew,
Isolation of three novel human cyclins by rescue of G1 cyclin (Cln) function in yeast.
1991,
Pubmed
Loog,
Cyclin specificity in the phosphorylation of cyclin-dependent kinase substrates.
2005,
Pubmed
Matsumoto,
Cyclin-dependent kinase 2 (Cdk2) is required for centrosome duplication in mammalian cells.
1999,
Pubmed
Meraldi,
Centrosome duplication in mammalian somatic cells requires E2F and Cdk2-cyclin A.
1999,
Pubmed
Meyerson,
A family of human cdc2-related protein kinases.
1992,
Pubmed
Moreno,
Regulation of p34cdc2 protein kinase during mitosis.
1989,
Pubmed
Nurse,
Gene required in G1 for commitment to cell cycle and in G2 for control of mitosis in fission yeast.
1981,
Pubmed
Ohtsubo,
Cyclin-dependent regulation of G1 in mammalian fibroblasts.
1993,
Pubmed
Ortega,
Cyclin-dependent kinase 2 is essential for meiosis but not for mitotic cell division in mice.
2003,
Pubmed
Paris,
Cloning by differential screening of a Xenopus cDNA coding for a protein highly homologous to cdc2.
1991,
Pubmed
,
Xenbase
Reed,
G1-specific cyclins: in search of an S-phase-promoting factor.
1991,
Pubmed
Santamaría,
Cdk1 is sufficient to drive the mammalian cell cycle.
2007,
Pubmed
Schwob,
CLB5 and CLB6, a new pair of B cyclins involved in DNA replication in Saccharomyces cerevisiae.
1993,
Pubmed
Sherr,
Living with or without cyclins and cyclin-dependent kinases.
2004,
Pubmed
Simanis,
The cell cycle control gene cdc2+ of fission yeast encodes a protein kinase potentially regulated by phosphorylation.
1986,
Pubmed
Stern,
A quantitative model for the cdc2 control of S phase and mitosis in fission yeast.
1996,
Pubmed
,
Xenbase
Tetsu,
Proliferation of cancer cells despite CDK2 inhibition.
2003,
Pubmed
Vassilev,
Selective small-molecule inhibitor reveals critical mitotic functions of human CDK1.
2006,
Pubmed
Vassilev,
Cell cycle synchronization at the G2/M phase border by reversible inhibition of CDK1.
2006,
Pubmed
Zhao,
NPAT links cyclin E-Cdk2 to the regulation of replication-dependent histone gene transcription.
2000,
Pubmed
van den Heuvel,
Distinct roles for cyclin-dependent kinases in cell cycle control.
1993,
Pubmed
