Regulation of the Atm promoter in vivo

Gueven, Nuri, Fukao, Toshiyuki, Luff, John, Paterson, Carol, Kay, Graham, Kondo, Naomi and Lavin, Martin F. (2006) Regulation of the Atm promoter in vivo. Genes Chromosomes & Cancer, 45 1: 61-71. doi:10.1002/gcc.20267


Author Gueven, Nuri
Fukao, Toshiyuki
Luff, John
Paterson, Carol
Kay, Graham
Kondo, Naomi
Lavin, Martin F.
Title Regulation of the Atm promoter in vivo
Journal name Genes Chromosomes & Cancer   Check publisher's open access policy
ISSN 1045-2257
Publication date 2006-01-01
Sub-type Article (original research)
DOI 10.1002/gcc.20267
Volume 45
Issue 1
Start page 61
End page 71
Total pages 11
Place of publication Hoboken
Publisher Wiley-liss
Language eng
Subject 11 Medical and Health Sciences
Abstract While ATM, the protein defective in the human genetic disorder ataxia-telangiectasia (A-T), is primarily activated as a preexisting protein by radiation, there is also evidence that expression of the protein can be regulated at the transcriptional level. Activation of the ATM promoter by ionizing radiation has been reported only in quiescent cells in culture. To investigate how the Atm promoter is regulated in vivo, we generated transgenic mice that express the luciferase reporter gene under the control of the murine Atm promoter. Using a biophotonic imaging system luciferase activity was monitored in vivo. Strong promoter activity was detected throughout the transgenic animals with particularly high signals from the thymus, abdominal region, and reproductive organs. This activity further increased in response to both ionizing radiation and heat stress in a time dependent manner. Luciferase activity, measured in vitro in extracts from different tissues, showed highest activities in testes, ovaries, and cerebellum. Subjecting these mice to a single dose of 4 Gy total body radiation led to a time-dependent activation of the promoter with the strongest response observed in the peritoneal membrane, skin, and spleen. For most tissues tested, maximal promoter activity was reached 8 hr after radiation. The observed changes in promoter activity largely correlated with levels and activity of Atm protein in tissue extracts. These results demonstrate that, in addition to activation by autophosphorylation, Atm can also be regulated in vivo at the transcriptional level possibly ensuring a more sustained response to radiation and other stimuli. (c) 2005 Wiley-Liss, Inc.
Keyword Oncology
Genetics & Heredity
Ataxia-telangiectasia Cells
Oxidative Stress
Deficient Mice
Dna-damage
Ionizing-radiation
Up-regulation
Gene-product
Wild-type
Protein
Autophosphorylation
Q-Index Code C1

Document type: Journal Article
Sub-type: Article (original research)
Collections: Excellence in Research Australia (ERA) - Collection
School of Medicine Publications
 
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Citation counts: TR Web of Science Citation Count  Cited 11 times in Thomson Reuters Web of Science Article | Citations
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Created: Thu, 18 Oct 2007, 00:10:09 EST