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Article: Blockade of TCFβ3 up-regulation of p27(Kip1) and p21(Cip1) by expression of RasN17 in epithelial cells

TitleBlockade of TCFβ3 up-regulation of p27(Kip1) and p21(Cip1) by expression of RasN17 in epithelial cells
Authors
Issue Date1998
PublisherNature Publishing Group. The Journal's web site is located at http://www.nature.com/onc
Citation
Oncogene, 1998, v. 17 n. 1, p. 47-55 How to Cite?
AbstractOur previous data demonstrated that Ras activation is necessary and sufficient for transforming growth factor β (TGFβ)-mediated Erk1 activation, and is partially required for the inhibition of cyclin-dependent kinase 2 (Cdk2) activity, cyclin A expression and DNA synthesis by TGFβ. Here, we examined the kinetics and role of Ras in TGFβ3-mediated effects on specific G1 cell cycle components in TGFβ-sensitive (4-1) acid TGFβ-resistant (4-6) intestinal epithelial cells (IEC's). Our results indicate that inactivation of Ras by stable, inducible expression of a dominant-negative mutant of Ras (RasN17) completely abrogated the ability of TGFβ3 to up-regulate both CKI's. In contrast, the ability of TGFβ3 to up-regulate p27(Kip1) and p21(Cip1) was maintained in ZnCl2-treated control cells. Inactivation of Ras also completely blocked the rapid TGFβ-mediated increase in new synthesis of p27(K)ip1) protein. Moreover, up-regulation of p21(Cip1) protein levels and new synthesis of p27(Kip1), as well as the association of these CKI's with Cdk2, preceded the decrease in Cdk2 activity by TGFβ. Collectively, our results suggest that p21(Cip1) and p27(Kip1) are upstream effecters of the TGFβ-mediated inhibition of Cdk2 activity in IEC 4-1 cells, and demonstrate that Ras activation is obligatory for TGFβ-mediated up-regulation of these CKIs in untransformed epithelial cells.
Persistent Identifierhttp://hdl.handle.net/10722/171654
ISSN
2015 Impact Factor: 7.932
2015 SCImago Journal Rankings: 4.047
ISI Accession Number ID
References

 

DC FieldValueLanguage
dc.contributor.authorYue, Jen_US
dc.contributor.authorBuard, Aen_US
dc.contributor.authorMulder, KMen_US
dc.date.accessioned2012-10-30T06:16:11Z-
dc.date.available2012-10-30T06:16:11Z-
dc.date.issued1998en_US
dc.identifier.citationOncogene, 1998, v. 17 n. 1, p. 47-55en_US
dc.identifier.issn0950-9232en_US
dc.identifier.urihttp://hdl.handle.net/10722/171654-
dc.description.abstractOur previous data demonstrated that Ras activation is necessary and sufficient for transforming growth factor β (TGFβ)-mediated Erk1 activation, and is partially required for the inhibition of cyclin-dependent kinase 2 (Cdk2) activity, cyclin A expression and DNA synthesis by TGFβ. Here, we examined the kinetics and role of Ras in TGFβ3-mediated effects on specific G1 cell cycle components in TGFβ-sensitive (4-1) acid TGFβ-resistant (4-6) intestinal epithelial cells (IEC's). Our results indicate that inactivation of Ras by stable, inducible expression of a dominant-negative mutant of Ras (RasN17) completely abrogated the ability of TGFβ3 to up-regulate both CKI's. In contrast, the ability of TGFβ3 to up-regulate p27(Kip1) and p21(Cip1) was maintained in ZnCl2-treated control cells. Inactivation of Ras also completely blocked the rapid TGFβ-mediated increase in new synthesis of p27(K)ip1) protein. Moreover, up-regulation of p21(Cip1) protein levels and new synthesis of p27(Kip1), as well as the association of these CKI's with Cdk2, preceded the decrease in Cdk2 activity by TGFβ. Collectively, our results suggest that p21(Cip1) and p27(Kip1) are upstream effecters of the TGFβ-mediated inhibition of Cdk2 activity in IEC 4-1 cells, and demonstrate that Ras activation is obligatory for TGFβ-mediated up-regulation of these CKIs in untransformed epithelial cells.en_US
dc.languageengen_US
dc.publisherNature Publishing Group. The Journal's web site is located at http://www.nature.com/oncen_US
dc.relation.ispartofOncogeneen_US
dc.subject.meshCdc2-Cdc28 Kinasesen_US
dc.subject.meshCell Cycle Proteinsen_US
dc.subject.meshCell Lineen_US
dc.subject.meshCyclin-Dependent Kinase 2en_US
dc.subject.meshCyclin-Dependent Kinase Inhibitor P21en_US
dc.subject.meshCyclin-Dependent Kinase Inhibitor P27en_US
dc.subject.meshCyclin-Dependent Kinases - Metabolismen_US
dc.subject.meshCyclins - Genetics - Metabolismen_US
dc.subject.meshDna - Biosynthesisen_US
dc.subject.meshEpithelial Cells - Drug Effects - Metabolismen_US
dc.subject.meshKineticsen_US
dc.subject.meshMicrotubule-Associated Proteins - Genetics - Metabolismen_US
dc.subject.meshProtein Kinases - Metabolismen_US
dc.subject.meshProtein-Serine-Threonine Kinases - Metabolismen_US
dc.subject.meshTransforming Growth Factor Beta - Metabolism - Pharmacologyen_US
dc.subject.meshTumor Suppressor Proteinsen_US
dc.subject.meshUp-Regulationen_US
dc.subject.meshRas Proteins - Genetics - Physiologyen_US
dc.titleBlockade of TCFβ3 up-regulation of p27(Kip1) and p21(Cip1) by expression of RasN17 in epithelial cellsen_US
dc.typeArticleen_US
dc.identifier.emailYue, J:jyue@hku.hken_US
dc.identifier.authorityYue, J=rp00286en_US
dc.description.naturelink_to_subscribed_fulltexten_US
dc.identifier.doi10.1038/sj.onc.1201903-
dc.identifier.pmid9671313-
dc.identifier.scopuseid_2-s2.0-0032499802en_US
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-0032499802&selection=ref&src=s&origin=recordpageen_US
dc.identifier.volume17en_US
dc.identifier.issue1en_US
dc.identifier.spage47en_US
dc.identifier.epage55en_US
dc.identifier.isiWOS:000074677800006-
dc.publisher.placeUnited Kingdomen_US
dc.identifier.scopusauthoridYue, J=7101875828en_US
dc.identifier.scopusauthoridBuard, A=6603503320en_US
dc.identifier.scopusauthoridMulder, KM=7005187184en_US

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