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DeltaNp63 transcriptionally regulates ATM to control p53 Serine-15 phosphorylation
Citation
Craig, AL and Holcakova, J and Finlan, LE and Nekulova, M and Hrstka, R and Guven, N and Smith, G and DiRenzo, J and Hupp, TR and Vojtesek, B, DeltaNp63 transcriptionally regulates ATM to control p53 Serine-15 phosphorylation, Molecular Cancer, 9, (195) pp. 1-13. ISSN 1476-4598 (2010) [Refereed Article]
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Licenced under Creative Commons Attribution 2.0 Generic (CC BY 2.0) http://creativecommons.org/licenses/by/2.0/
DOI: doi:10.1186/1476-4598-9-195
Abstract
Abstract
Background: ÄNp63á is an epithelial progenitor cell marker that maintains epidermal stem cell self-renewal capacity.Previous studies revealed that UV-damage induced p53 phosphorylation is confined to ÄNp63á-positive cells in the
basal layer of human epithelium.
Results: We now report that phosphorylation of the p53 tumour suppressor is positively regulated by ÄNp63á in immortalised human keratinocytes. ÄNp63á depletion by RNAi reduces steady-state ATM mRNA and protein levels,
and attenuates p53 Serine-15 phosphorylation. Conversely, ectopic expression of ÄNp63á in p63-null tumour cells stimulates ATM transcription and p53 Serine-15 phosphorylation. We show that ATM is a direct ÄNp63á transcriptional
target and that the ÄNp63á response element localizes to the ATM promoter CCAAT sequence. Structure-function analysis revealed that the ÄNp63-specific TA2 transactivation domain mediates ATM transcription in coordination with
the DNA binding and SAM domains.
Conclusions: Germline p63 point mutations are associated with a range of ectodermal developmental disorders, and targeted p63 deletion in the skin causes premature ageing. The ÄNp63á-ATM-p53 damage-response pathway may
therefore function in epithelial development, carcinogenesis and the ageing processes.
Item Details
Item Type: | Refereed Article |
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Keywords: | ATM, p53, p63 phosphorylation |
Research Division: | Biological Sciences |
Research Group: | Biochemistry and cell biology |
Research Field: | Signal transduction |
Objective Division: | Expanding Knowledge |
Objective Group: | Expanding knowledge |
Objective Field: | Expanding knowledge in the biological sciences |
UTAS Author: | Guven, N (Dr Nuri Guven) |
ID Code: | 79272 |
Year Published: | 2010 |
Web of Science® Times Cited: | 26 |
Deposited By: | Pharmacy |
Deposited On: | 2012-08-29 |
Last Modified: | 2012-11-05 |
Downloads: | 532 View Download Statistics |
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