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dc.contributor.authorD'Abaco, GM
dc.contributor.authorHooper, S
dc.contributor.authorPaterson, H
dc.contributor.authorMarshall, CJ
dc.date.accessioned2018-06-05T13:32:52Z
dc.date.issued2002-12
dc.identifier.citationJournal of cell science, 2002, 115 (Pt 23), pp. 4607 - 4616
dc.identifier.issn0021-9533
dc.identifier.urihttps://repository.icr.ac.uk/handle/internal/1714
dc.identifier.eissn1477-9137
dc.identifier.doi10.1242/jcs.00161
dc.description.abstractThe Ras GTPase is a critical transducer of mitogenic signals ultimately leading to inactivation of the retinoblastoma (Rb) protein, but the molecular basis underlying Ras-dependent control of cell cycle kinetics remains to a great extent unknown. In an effort to further elucidate the role of Ras activation in cell cycle control, we have studied the role of the downstream Mek-ERK pathway in facilitating exit from the quiescent G0 state and passage through the G1/S transition. We have adopted a genetic approach in combination with U0126, an inhibitor of Mek activation to study the role of Mek in cell cycle progression. Here we report that whereas wild-type (Wt) mouse embryo fibroblasts (MEFs) depend on ERK activation to enter the cell cycle, Rb-deficient (Rb(-/-)) MEFs have a reduced requirement for ERK signalling. Indeed in the presence of U0126 we found that Rb-null MEFs can exit G0, make the G1/S transition and proliferate. Analysis of Rb-deficient tumour cell lines also revealed a reduced requirement for ERK signalling in asynchronous growth. We discuss the molecular mechanism that may underlie this escape from MAP kinase signalling.
dc.formatPrint
dc.format.extent4607 - 4616
dc.languageeng
dc.language.isoeng
dc.subjectCells, Cultured
dc.subjectTumor Cells, Cultured
dc.subjectAnimals
dc.subjectMice
dc.subjectButadienes
dc.subjectNitriles
dc.subjectMorpholines
dc.subjectChromones
dc.subjectCyclin-Dependent Kinases
dc.subjectMitogen-Activated Protein Kinase Kinases
dc.subjectMitogen-Activated Protein Kinases
dc.subjectCyclins
dc.subjectRetinoblastoma Protein
dc.subjectProto-Oncogene Proteins
dc.subjectCell Division
dc.subjectMAP Kinase Signaling System
dc.subjectGene Expression Regulation
dc.subjectGene Deletion
dc.subjectPhosphorylation
dc.subjectTime Factors
dc.subjectCyclin-Dependent Kinase 4
dc.subjectPhosphatidylinositol 3-Kinases
dc.titleLoss of Rb overrides the requirement for ERK activity for cell proliferation.
dc.typeJournal Article
rioxxterms.versionofrecord10.1242/jcs.00161
rioxxterms.licenseref.startdate2002-12
rioxxterms.typeJournal Article/Review
dc.relation.isPartOfJournal of cell science
pubs.issuePt 23
pubs.notesNot known
pubs.organisational-group/ICR
pubs.organisational-group/ICR/Primary Group
pubs.organisational-group/ICR/Primary Group/ICR Divisions
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Closed research teams
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Closed research teams/Oncogene
pubs.organisational-group/ICR
pubs.organisational-group/ICR/Primary Group
pubs.organisational-group/ICR/Primary Group/ICR Divisions
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Closed research teams
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Closed research teams/Oncogene
pubs.publication-statusPublished
pubs.volume115
pubs.embargo.termsNot known
icr.researchteamOncogeneen_US
dc.contributor.icrauthorMarshall, Christopheren


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