Click here to close
Hello! We notice that you are using Internet Explorer, which is not supported by Xenbase and may cause the site to display incorrectly.
We suggest using a current version of Chrome,
FireFox, or Safari.
???displayArticle.abstract???
Proliferating eukaryotic cells possess checkpoint mechanisms that block cell division in the presence of unreplicated or damaged DNA. Using cell-free extracts from Xenopus eggs, we have investigated the mechanisms underlying the inability of a recombinant Cdc2/cyclin B complex to induce mitosis in the presence of incompletely replicated DNA. We found that the activities of the kinases and phosphatases that regulate the major phosphorylation sites on Cdc2 (e.g., tyrosine 15, threonine 14, and threonine 161) are not altered significantly under conditions where Xenopus extracts remain stably arrested in interphase due to the presence of the replication inhibitor aphidicolin. However, at threshold concentrations, a Cdc2/cyclin B complex containing a mutant Cdc2 subunit that cannot be phosphorylated on either tyrosine 15 or threonine 14 displays a markedly reduced capacity to induce mitosis in the presence of aphidicolin. This observation indicates that the replication checkpoint in Xenopus egg extracts functions without the inhibitory tyrosine and threonine phosphorylation of Cdc2. We provide evidence that the checkpoint-dependent suppression of the Cdc2/cyclin B complex involves a titratable inhibitor that is regulated by the presence of unreplicated DNA.
Amon,
Regulation of p34CDC28 tyrosine phosphorylation is not required for entry into mitosis in S. cerevisiae.
1992, Pubmed,
Xenbase
Amon,
Regulation of p34CDC28 tyrosine phosphorylation is not required for entry into mitosis in S. cerevisiae.
1992,
Pubmed
,
Xenbase Barbet,
Fission yeast wee1 protein kinase is not required for DNA damage-dependent mitotic arrest.
1993,
Pubmed Booher,
Properties of Saccharomyces cerevisiae wee1 and its differential regulation of p34CDC28 in response to G1 and G2 cyclins.
1993,
Pubmed Boyle,
Phosphopeptide mapping and phosphoamino acid analysis by two-dimensional separation on thin-layer cellulose plates.
1991,
Pubmed Brown,
Expression and activity of p40MO15, the catalytic subunit of cdk-activating kinase, during Xenopus oogenesis and embryogenesis.
1994,
Pubmed
,
Xenbase Clarke,
Dephosphorylation of cdc25-C by a type-2A protein phosphatase: specific regulation during the cell cycle in Xenopus egg extracts.
1993,
Pubmed
,
Xenbase Coleman,
Negative regulation of the wee1 protein kinase by direct action of the nim1/cdr1 mitotic inducer.
1993,
Pubmed Connell-Crowley,
Phosphorylation independent activation of human cyclin-dependent kinase 2 by cyclin A in vitro.
1993,
Pubmed
,
Xenbase Dasso,
Completion of DNA replication is monitored by a feedback system that controls the initiation of mitosis in vitro: studies in Xenopus.
1990,
Pubmed
,
Xenbase Desai,
Activation of human cyclin-dependent kinases in vitro.
1992,
Pubmed Draetta,
Cdc2 activation: the interplay of cyclin binding and Thr161 phosphorylation.
1993,
Pubmed Dunphy,
The decision to enter mitosis.
1994,
Pubmed Dunphy,
The cdc25 protein contains an intrinsic phosphatase activity.
1991,
Pubmed Dunphy,
Fission yeast p13 blocks mitotic activation and tyrosine dephosphorylation of the Xenopus cdc2 protein kinase.
1989,
Pubmed
,
Xenbase Enoch,
Mutation of fission yeast cell cycle control genes abolishes dependence of mitosis on DNA replication.
1990,
Pubmed Enoch,
Fission yeast genes involved in coupling mitosis to completion of DNA replication.
1992,
Pubmed Enoch,
Mitotic checkpoint control in fission yeast.
1991,
Pubmed Fleig,
Regulation of cdc2 activity in Schizosaccharomyces pombe: the role of phosphorylation.
1991,
Pubmed Galaktionov,
Specific activation of cdc25 tyrosine phosphatases by B-type cyclins: evidence for multiple roles of mitotic cyclins.
1991,
Pubmed Gautier,
cdc25 is a specific tyrosine phosphatase that directly activates p34cdc2.
1991,
Pubmed
,
Xenbase Glotzer,
Cyclin is degraded by the ubiquitin pathway.
1991,
Pubmed
,
Xenbase Gould,
Tyrosine phosphorylation of the fission yeast cdc2+ protein kinase regulates entry into mitosis.
1989,
Pubmed Hartwell,
Checkpoints: controls that ensure the order of cell cycle events.
1989,
Pubmed Izumi,
Periodic changes in phosphorylation of the Xenopus cdc25 phosphatase regulate its activity.
1992,
Pubmed
,
Xenbase Izumi,
Elimination of cdc2 phosphorylation sites in the cdc25 phosphatase blocks initiation of M-phase.
1993,
Pubmed
,
Xenbase Kobayashi,
On the synthesis and destruction of A- and B-type cyclins during oogenesis and meiotic maturation in Xenopus laevis.
1991,
Pubmed
,
Xenbase Kornbluth,
In vitro cell cycle arrest induced by using artificial DNA templates.
1992,
Pubmed
,
Xenbase Kornbluth,
Membrane localization of the kinase which phosphorylates p34cdc2 on threonine 14.
1994,
Pubmed
,
Xenbase Krek,
Differential phosphorylation of vertebrate p34cdc2 kinase at the G1/S and G2/M transitions of the cell cycle: identification of major phosphorylation sites.
1991,
Pubmed Kuang,
cdc25 is one of the MPM-2 antigens involved in the activation of maturation-promoting factor.
1994,
Pubmed
,
Xenbase Kumagai,
Regulation of the cdc25 protein during the cell cycle in Xenopus extracts.
1992,
Pubmed
,
Xenbase Kumagai,
The cdc25 protein controls tyrosine dephosphorylation of the cdc2 protein in a cell-free system.
1991,
Pubmed
,
Xenbase Lee,
Inhibition of cdc2 activation by INH/PP2A.
1994,
Pubmed
,
Xenbase Lorca,
Dephosphorylation of cdc2 on threonine 161 is required for cdc2 kinase inactivation and normal anaphase.
1992,
Pubmed
,
Xenbase Lundgren,
mik1 and wee1 cooperate in the inhibitory tyrosine phosphorylation of cdc2.
1991,
Pubmed McGowan,
Human Wee1 kinase inhibits cell division by phosphorylating p34cdc2 exclusively on Tyr15.
1993,
Pubmed Milarski,
Cloning and characterization of Xenopus cdc2, a component of MPF.
1991,
Pubmed
,
Xenbase Morla,
Reversible tyrosine phosphorylation of cdc2: dephosphorylation accompanies activation during entry into mitosis.
1989,
Pubmed Mueller,
Cell cycle regulation of a Xenopus Wee1-like kinase.
1995,
Pubmed
,
Xenbase Murray,
Cell cycle extracts.
1991,
Pubmed Murray,
Creative blocks: cell-cycle checkpoints and feedback controls.
1992,
Pubmed Murray,
Cyclin synthesis drives the early embryonic cell cycle.
1989,
Pubmed
,
Xenbase Nigg,
Cellular substrates of p34(cdc2) and its companion cyclin-dependent kinases.
1993,
Pubmed Norbury,
Regulatory phosphorylation of the p34cdc2 protein kinase in vertebrates.
1991,
Pubmed
,
Xenbase Nurse,
Universal control mechanism regulating onset of M-phase.
1990,
Pubmed Parker,
Inactivation of the p34cdc2-cyclin B complex by the human WEE1 tyrosine kinase.
1992,
Pubmed Pines,
Cyclins and cyclin-dependent kinases: take your partners.
1993,
Pubmed Pines,
Isolation of a human cyclin cDNA: evidence for cyclin mRNA and protein regulation in the cell cycle and for interaction with p34cdc2.
1989,
Pubmed Rowley,
The wee1 protein kinase is required for radiation-induced mitotic delay.
1992,
Pubmed Russell,
cdc25+ functions as an inducer in the mitotic control of fission yeast.
1986,
Pubmed Russell,
Negative regulation of mitosis by wee1+, a gene encoding a protein kinase homolog.
1987,
Pubmed Schlegel,
Periodic mitotic events induced in the absence of DNA replication.
1987,
Pubmed Sebastian,
Cdc25M2 activation of cyclin-dependent kinases by dephosphorylation of threonine-14 and tyrosine-15.
1993,
Pubmed Sheldrick,
Feedback controls and G2 checkpoints: fission yeast as a model system.
1993,
Pubmed Smythe,
Coupling of mitosis to the completion of S phase in Xenopus occurs via modulation of the tyrosine kinase that phosphorylates p34cdc2.
1992,
Pubmed
,
Xenbase Solomon,
Cyclin activation of p34cdc2.
1990,
Pubmed
,
Xenbase Solomon,
Activation of the various cyclin/cdc2 protein kinases.
1993,
Pubmed Solomon,
Role of phosphorylation in p34cdc2 activation: identification of an activating kinase.
1992,
Pubmed
,
Xenbase Sorger,
S-phase feedback control in budding yeast independent of tyrosine phosphorylation of p34cdc28.
1992,
Pubmed
,
Xenbase Stueland,
Full activation of p34CDC28 histone H1 kinase activity is unable to promote entry into mitosis in checkpoint-arrested cells of the yeast Saccharomyces cerevisiae.
1993,
Pubmed
,
Xenbase Tang,
Two distinct mechanisms for negative regulation of the Wee1 protein kinase.
1993,
Pubmed
,
Xenbase
