Rapid radiation-induction of atm protein levels in situ

Fang, ZM, Lee, CS, Sarris, M, Kearsley, JH, Murrell, D, Lavin, MF, Keating, K and Clarke, RA (2001) Rapid radiation-induction of atm protein levels in situ. Pathology, 33 1: 30-36.

Author Fang, ZM
Lee, CS
Sarris, M
Kearsley, JH
Murrell, D
Lavin, MF
Keating, K
Clarke, RA
Title Rapid radiation-induction of atm protein levels in situ
Journal name Pathology   Check publisher's open access policy
ISSN 0031-3025
Publication date 2001-01-01
Sub-type Article (original research)
Volume 33
Issue 1
Start page 30
End page 36
Total pages 7
Place of publication Basingstoke UK
Publisher Carfax Publishing Limited
Collection year 2001
Language eng
Subject C1
270103 Protein Targeting and Signal Transduction
730108 Cancer and related disorders
Abstract Ataxia-telangiectasia (A-T) is characterised by hypersensitivity to ionising radiation (IR), immunodeficiency, neurodegeneration and predisposition to malignancy. Mutations in the A-T gene (ATM) often result in reduced levels of ATM protein and/or compromise ATM function. IR induced DNA damage is known to rapidly upregulate ATM kinase activity/phosphorylation events in the control of cell cycle progression and other processes. Variable expression of ATM levels in different tissues and its upregulation during cellular proliferation indicate that the level of ATM is also regulated by mechanisms other than gene mutation. Here, we report on the IR induction of ATM protein levels within a number of different cell types and tissues. Induction had begun within 5 min and peaked within 2 h of exposure to 2 Gy of IR, suggesting a rapid post-translational mechanism. Low basal levels of ATM protein were more responsive to IR induction compared to high ATM levels in the same cell type. Irradiation of fresh skin biopsies led to an average three-fold increase in ATM levels while immunohistochemical analyses indicated low expressing cells within the basal layer with ten-fold increases in ATM levels following IR. ATM high expressing lymphoblastoid cell lines (LCLs) which were initially resistant to the radiation-induction of ATM levels also became responsive to IR after ATM antisense expression was used to reduce the basal levels of the protein. These results demonstrate that ATM is present in variable amounts in different tissue/cell types and where basal levels are low ATM levels can be rapidly induced by IR to saturable levels specific for different cell types. ATM radiation-induction is a sensitive and rapid radioprotective response that complements the IR mediated activation of ATM.
Keyword Pathology
Ataxia-telangiectasia
Atm
Radiation-induction
Protein Level
Protein Regulation
Radiosensitivity
Radio-protection
Cancer
Cycle Checkpoint Pathway
Dna-damage
Gene-product
Signal-transduction
P53
Phosphorylation
Kinase
Defect
Cells
Q-Index Code C1

Document type: Journal Article
Sub-type: Article (original research)
Collection: School of Medicine Publications
 
Versions
Version Filter Type
Citation counts: TR Web of Science Citation Count  Cited 10 times in Thomson Reuters Web of Science Article | Citations
Google Scholar Search Google Scholar
Created: Wed, 15 Aug 2007, 01:56:29 EST