ATM is upregulated during the mitogenic response in peripheral blood mononuclear cells

Fukao, Toshiyuki, Kaneko, Hideo, Birrell, Geoff, Gatei, Magtouf, Tashita, Hideaki, Yoshida, Toko, Cross, Simone, Kedar, Padmini, Watters, Dianne, Khana, Kum Kum, Misko, Ihor, Kondo, Naomi and Lavin, Martin F. (1999) ATM is upregulated during the mitogenic response in peripheral blood mononuclear cells. Blood, 94 6: 1998-2006.

Author Fukao, Toshiyuki
Kaneko, Hideo
Birrell, Geoff
Gatei, Magtouf
Tashita, Hideaki
Yoshida, Toko
Cross, Simone
Kedar, Padmini
Watters, Dianne
Khana, Kum Kum
Misko, Ihor
Kondo, Naomi
Lavin, Martin F.
Title ATM is upregulated during the mitogenic response in peripheral blood mononuclear cells
Journal name Blood   Check publisher's open access policy
ISSN 0006-4971
Publication date 1999-09-15
Sub-type Article (original research)
Volume 94
Issue 6
Start page 1998
End page 2006
Total pages 9
Place of publication New York
Publisher Stratton
Collection year 1999
Language eng
Subject C1
321015 Oncology and Carcinogenesis
730108 Cancer and related disorders
Abstract Patients with the human genetic disorder ataxia-telangiectasia (A-T) are characterized by immunodeficiency and a predisposition to develop lymphoid malignancies. The gene mutated in A-T patients, ATM codes for a high molecular weight protein that is implicated in DNA damage recognition and cell cycle control. The ATM protein does not change in amount or cellular distribution throughout the cell cycle or in response to DNA damaging agents. Because peripheral blood mononuclear cells (PBMCs) are largely in a state of quiescence and can be readily stimulated to enter a proliferative phase and because A-T cells exhibit growth abnormalities and senescence, indicative of a general intracellular defect in signalling, we chose PBMCs to examine the relationship of ATM to the proliferative status of the cell. We show here that ATM protein is present at low levels in freshly isolated PBMCs and increases approximately 6-fold to 10-fold in response to a mitogenic stimulus, reaching a maximum after 3 to 4 days. A similar, but delayed response, was evident in the presence of serum only, This increase in ATM protein was accompanied by an increase in ATM kinase activity, While expression of ATM protein increased during proliferation, ATM mRNA expression was unchanged in stimulated and unstimulated cells and there was no evidence for increased ATM protein stability in the phytohemagglutinin (PHA)-treated cells. In keeping with the reduced levels of ATM in quiescent cells, the extent of radiation-induction of the p53 pathway was significantly lower than in mitogen-stimulated cells. Basal levels of p21 were elevated in quiescent cells, and the response to radiation was negligible or reduced compared with proliferating cells over a P-hour period, Overall, the data suggest that the increase in ATM protein in proliferating cells is due to posttranscriptional regulation and points to a role for ATM in more general signalling. (C) 1999 by The American Society of Hematology.
Keyword Hematology
Ataxia-telangiectasia Gene
Ionizing-radiation
Prolymphocytic Leukemia
Up-regulation
P53 Protein
Dna-damage
Lymphocytes
Product
Recombination
Expression
Q-Index Code C1

Document type: Journal Article
Sub-type: Article (original research)
Collection: School of Medicine Publications
 
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Created: Wed, 11 Jun 2008, 01:16:32 EST