dc.contributor.author | Keating, KE | |
dc.contributor.author | Gueven, N | |
dc.contributor.author | Watters, D | |
dc.contributor.author | Rodemann, HP | |
dc.contributor.author | Lavin, MF | |
dc.date.accessioned | 2017-05-03T12:20:07Z | |
dc.date.available | 2017-05-03T12:20:07Z | |
dc.date.issued | 2001 | |
dc.date.modified | 2008-02-14T08:25:14Z | |
dc.identifier.issn | 0950-9232 | |
dc.identifier.uri | http://hdl.handle.net/10072/16931 | |
dc.description.abstract | There 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.peerreviewed | Yes | |
dc.description.publicationstatus | Yes | |
dc.language | English | |
dc.language.iso | eng | |
dc.publisher | Nature Publishing Group | |
dc.publisher.place | Hampshire, England | |
dc.relation.ispartofpagefrom | 4281 | |
dc.relation.ispartofpageto | 4290 | |
dc.relation.ispartofjournal | Oncogene | |
dc.relation.ispartofvolume | 20 | |
dc.subject.fieldofresearch | Clinical sciences | |
dc.subject.fieldofresearch | Oncology and carcinogenesis | |
dc.subject.fieldofresearchcode | 3202 | |
dc.subject.fieldofresearchcode | 3211 | |
dc.title | Transcriptional downregulation of ATM by EGF is defective in ataxia-telangiectasia cells expressing mutant protein | |
dc.type | Journal article | |
dc.type.description | C1 - Articles | |
dc.type.code | C - Journal Articles | |
gro.date.issued | 2001 | |
gro.hasfulltext | No Full Text | |
gro.griffith.author | Watters, Dianne J. | |