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.
Oncogenic Ras suppresses Cdk1 in a complex manner during the incubation of activated Xenopus egg extracts.
Huang TL
,
Pian JP
,
Pan BT
.
???displayArticle.abstract???
The activity of Cdk1 is the driving force for entry into M-phase during the cell cycle. Activation of Cdk1 requires synthesis and accumulation of cyclin B, binding of cyclin B to Cdk1, and removal of the inhibitory tyr-15-Cdk1 phosphorylation. It was previously shown that oncogenic Ras suppresses Cdk1 activation during the incubation of activated Xenopus egg extracts. However, how oncogenic Ras suppresses Cdk1 remained unclear. Using the histone H1 kinase assay to follow Cdk1 activity and Western blot analysis to assess levels of both cyclin B2 and phosphorylated-tyr-15-Cdk1, how oncogenic Ras suppresses Cdk1 is studied. The results indicate that oncogenic Ras suppresses Cdk1 via induction of persistent phosphorylation of tyr-15-Cdk1. Interestingly, the results reveal that, compared with cyclin B2 in control activated egg extracts, which increased, peaked and then declined during the incubation, oncogenic Ras induced continuous accumulation of cyclin B2. The results also indicate that oncogenic Ras induces continuous accumulation of cyclin B2 primarily through stabilization of cyclin B2, which is mediated by constitutive activation of the Raf-Mek-Erk-p90(rsk) pathway. Taken together, these results indicate that oncogenic Ras suppresses Cdk1 in a complex manner: It induces continuous accumulation of cyclin B2, but also causes persistent inhibitory phosphorylation of tyr-15-Cdk1.
Abrieu,
MAPK inactivation is required for the G2 to M-phase transition of the first mitotic cell cycle.
1997, Pubmed,
Xenbase
Abrieu,
MAPK inactivation is required for the G2 to M-phase transition of the first mitotic cell cycle.
1997,
Pubmed
,
Xenbase
Bhatt,
The protein kinase p90 rsk as an essential mediator of cytostatic factor activity.
1999,
Pubmed
,
Xenbase
Bhatt,
Cloning and characterization of Xenopus Rsk2, the predominant p90 Rsk isozyme in oocytes and eggs.
2000,
Pubmed
,
Xenbase
Bitangcol,
Activation of the p42 mitogen-activated protein kinase pathway inhibits Cdc2 activation and entry into M-phase in cycling Xenopus egg extracts.
1998,
Pubmed
,
Xenbase
Bodart,
Activation of Xenopus eggs by the kinase inhibitor 6-DMAP suggests a differential regulation of cyclin B and p39(mos) proteolysis.
1999,
Pubmed
,
Xenbase
Chen,
Dual-specific Cdc25B phosphatase: in search of the catalytic acid.
2000,
Pubmed
,
Xenbase
Chun,
Phosphorylation of Cdc25C by pp90Rsk contributes to a G2 cell cycle arrest in Xenopus cycling egg extracts.
2005,
Pubmed
,
Xenbase
Daar,
The ras oncoprotein and M-phase activity.
1991,
Pubmed
,
Xenbase
Dorée,
From Cdc2 to Cdk1: when did the cell cycle kinase join its cyclin partner?
2002,
Pubmed
Downward,
Targeting RAS signalling pathways in cancer therapy.
2003,
Pubmed
Dunphy,
The Xenopus cdc2 protein is a component of MPF, a cytoplasmic regulator of mitosis.
1988,
Pubmed
,
Xenbase
Erikson,
In vivo phosphorylation and activation of ribosomal protein S6 kinases during Xenopus oocyte maturation.
1989,
Pubmed
,
Xenbase
Favata,
Identification of a novel inhibitor of mitogen-activated protein kinase kinase.
1998,
Pubmed
Fukuda,
Analysis of the Ras p21/mitogen-activated protein kinase signaling in vitro and in Xenopus oocytes.
1994,
Pubmed
,
Xenbase
Gautier,
cdc25 is a specific tyrosine phosphatase that directly activates p34cdc2.
1991,
Pubmed
,
Xenbase
Glickman,
The ubiquitin-proteasome proteolytic pathway: destruction for the sake of construction.
2002,
Pubmed
Glotzer,
Cyclin is degraded by the ubiquitin pathway.
1991,
Pubmed
,
Xenbase
Gross,
The critical role of the MAP kinase pathway in meiosis II in Xenopus oocytes is mediated by p90(Rsk).
2000,
Pubmed
,
Xenbase
Hershko,
Mechanisms and regulation of the degradation of cyclin B.
1999,
Pubmed
,
Xenbase
Hirakawa,
Rescue of cells from ras oncogene-induced growth arrest by a second, complementing, oncogene.
1988,
Pubmed
Itoh,
A protein factor for ras p21-dependent activation of mitogen-activated protein (MAP) kinase through MAP kinase kinase.
1993,
Pubmed
,
Xenbase
King,
A 20S complex containing CDC27 and CDC16 catalyzes the mitosis-specific conjugation of ubiquitin to cyclin B.
1995,
Pubmed
,
Xenbase
Kraft,
Mitotic regulation of the human anaphase-promoting complex by phosphorylation.
2003,
Pubmed
Kumagai,
The cdc25 protein controls tyrosine dephosphorylation of the cdc2 protein in a cell-free system.
1991,
Pubmed
,
Xenbase
Lahav-Baratz,
Reversible phosphorylation controls the activity of cyclosome-associated cyclin-ubiquitin ligase.
1995,
Pubmed
Land,
Tumorigenic conversion of primary embryo fibroblasts requires at least two cooperating oncogenes.
,
Pubmed
Lin,
Premature senescence involving p53 and p16 is activated in response to constitutive MEK/MAPK mitogenic signaling.
1998,
Pubmed
Lloyd,
Ras versus cyclin-dependent kinase inhibitors.
1998,
Pubmed
Maller,
Maturation-promoting factor and the regulation of the cell cycle.
1989,
Pubmed
,
Xenbase
Malumbres,
RAS oncogenes: the first 30 years.
2003,
Pubmed
Minshull,
Translation of cyclin mRNA is necessary for extracts of activated xenopus eggs to enter mitosis.
1989,
Pubmed
,
Xenbase
Moore,
Identification of the nuclear localization signal in Xenopus cyclin E and analysis of its role in replication and mitosis.
2002,
Pubmed
,
Xenbase
Morgan,
Principles of CDK regulation.
1995,
Pubmed
Mueller,
Myt1: a membrane-associated inhibitory kinase that phosphorylates Cdc2 on both threonine-14 and tyrosine-15.
1995,
Pubmed
,
Xenbase
Murakami,
Analysis of the early embryonic cell cycles of Xenopus; regulation of cell cycle length by Xe-wee1 and Mos.
1998,
Pubmed
,
Xenbase
Murray,
Cyclin synthesis drives the early embryonic cell cycle.
1989,
Pubmed
,
Xenbase
Nilsson,
Cell cycle regulation by the Cdc25 phosphatase family.
2000,
Pubmed
Nurse,
Universal control mechanism regulating onset of M-phase.
1990,
Pubmed
Pan,
Oncogenic Ras blocks cell cycle progression and inhibits p34cdc2 kinase in activated Xenopus egg extracts.
1994,
Pubmed
,
Xenbase
Pan,
Role of phosphatidylinositide metabolism in ras-induced Xenopus oocyte maturation.
1990,
Pubmed
,
Xenbase
Parker,
Inactivation of the p34cdc2-cyclin B complex by the human WEE1 tyrosine kinase.
1992,
Pubmed
Philpott,
The Xenopus cell cycle: an overview.
2008,
Pubmed
,
Xenbase
Pian,
A 32 kDa protein--whose phosphorylation correlates with oncogenic Ras-induced cell cycle arrest in activated Xenopus egg extracts--is identified as ribosomal protein S6.
2004,
Pubmed
,
Xenbase
Ridley,
Ras-mediated cell cycle arrest is altered by nuclear oncogenes to induce Schwann cell transformation.
1988,
Pubmed
Roberts,
Targeting the Raf-MEK-ERK mitogen-activated protein kinase cascade for the treatment of cancer.
2007,
Pubmed
Romeo,
Regulation and function of the RSK family of protein kinases.
2012,
Pubmed
Rudner,
Phosphorylation by Cdc28 activates the Cdc20-dependent activity of the anaphase-promoting complex.
2000,
Pubmed
Rudolph,
Cdc25 phosphatases: structure, specificity, and mechanism.
2007,
Pubmed
Russell,
Negative regulation of mitosis by wee1+, a gene encoding a protein kinase homolog.
1987,
Pubmed
Russell,
cdc25+ functions as an inducer in the mitotic control of fission yeast.
1986,
Pubmed
Serrano,
Oncogenic ras provokes premature cell senescence associated with accumulation of p53 and p16INK4a.
1997,
Pubmed
Sherr,
CDK inhibitors: positive and negative regulators of G1-phase progression.
1999,
Pubmed
Shibuya,
Oncogenic ras triggers the activation of 42-kDa mitogen-activated protein kinase in extracts of quiescent Xenopus oocytes.
1992,
Pubmed
,
Xenbase
Sohn,
Remote hot spots mediate protein substrate recognition for the Cdc25 phosphatase.
2004,
Pubmed
,
Xenbase
Strausfeld,
Dephosphorylation and activation of a p34cdc2/cyclin B complex in vitro by human CDC25 protein.
1991,
Pubmed
Sudakin,
The cyclosome, a large complex containing cyclin-selective ubiquitin ligase activity, targets cyclins for destruction at the end of mitosis.
1995,
Pubmed
VanRenterghem,
Reconstitution of p21ras-dependent and -independent mitogen-activated protein kinase activation in a cell-free system.
1993,
Pubmed
,
Xenbase
Walter,
Activation of Wee1 by p42 MAPK in vitro and in cycling xenopus egg extracts.
2000,
Pubmed
,
Xenbase
Yue,
B-Raf and C-Raf are required for Ras-stimulated p42 MAP kinase activation in Xenopus egg extracts.
2006,
Pubmed
,
Xenbase
Zachariae,
Whose end is destruction: cell division and the anaphase-promoting complex.
1999,
Pubmed
