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dc.contributor.authorKeating, KE
dc.contributor.authorGueven, N
dc.contributor.authorWatters, D
dc.contributor.authorRodemann, HP
dc.contributor.authorLavin, MF
dc.date.accessioned2017-05-03T12:20:07Z
dc.date.available2017-05-03T12:20:07Z
dc.date.issued2001
dc.date.modified2008-02-14T08:25:14Z
dc.identifier.issn0950-9232
dc.identifier.urihttp://hdl.handle.net/10072/16931
dc.description.abstractThere is evidence that ATM plays a wider role in intracellular signalling in addition to DNA damage recognition and cell cycle control, In this report we show that activation of the EGF receptor is defective in ataxia-telangiectasia (A-T) cells and that sustained stimulation of cells with EGF downregulates ATM protein in control cells but not in A-T cells expressing mutant protein, Concomitant with the downregulation of ATM, DNA-binding activity of the transcription factor Spl decreased in controls after EGF treatment but increased from a lower basal level in A-T cells to that in untreated control cells, Mutation in two Spl consensus sequences in the ATM promoter reduced markedly the capacity of the promoter to support luciferase activity in a reporter assay. Overexpression of anti-sense ATM cDNA in control cells decreased the;basal level of Spl, which in turn was increased by subsequent treatment of cells with EGF, similar to that observed in,A-T cells. On the other hand full-length ATM cDNA increased the basal level of Spl binding in A-T cells, and in response to EGF Spl binding decreased, confirming that this is an ATR I-dependent process. Contrary to that observed in control cells there was no radiation-induced change in ATM protein in EGF-treated A-T cells and likewise no alteration in Spl binding activity. The results demonstrate that EGF-induced downregulation of ATM (mutant) protein in A-T cells is defective and this appears to be due to less efficient EGFR activation and abnormal Spl regulation.
dc.description.peerreviewedYes
dc.description.publicationstatusYes
dc.languageEnglish
dc.language.isoeng
dc.publisherNature Publishing Group
dc.publisher.placeHampshire, England
dc.relation.ispartofpagefrom4281
dc.relation.ispartofpageto4290
dc.relation.ispartofjournalOncogene
dc.relation.ispartofvolume20
dc.subject.fieldofresearchClinical sciences
dc.subject.fieldofresearchOncology and carcinogenesis
dc.subject.fieldofresearchcode3202
dc.subject.fieldofresearchcode3211
dc.titleTranscriptional downregulation of ATM by EGF is defective in ataxia-telangiectasia cells expressing mutant protein
dc.typeJournal article
dc.type.descriptionC1 - Articles
dc.type.codeC - Journal Articles
gro.date.issued2001
gro.hasfulltextNo Full Text
gro.griffith.authorWatters, Dianne J.


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