The plant isoflavenoid genistein activates p53 and Chk2 in an ATM-dependent manner

Ye, RQ, Bodero, A, Zhou, BB, Khanna, KK, Lavin, MF and Lees-Miller, SP (2001) The plant isoflavenoid genistein activates p53 and Chk2 in an ATM-dependent manner. Journal of Biological Chemistry, 276 7: 4828-4833. doi:10.1074/jbc.M004894200

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Author Ye, RQ
Bodero, A
Zhou, BB
Khanna, KK
Lavin, MF
Lees-Miller, SP
Title The plant isoflavenoid genistein activates p53 and Chk2 in an ATM-dependent manner
Journal name Journal of Biological Chemistry   Check publisher's open access policy
ISSN 0021-9258
Publication date 2001-01-01
Sub-type Article (original research)
DOI 10.1074/jbc.M004894200
Open Access Status File (Publisher version)
Volume 276
Issue 7
Start page 4828
End page 4833
Total pages 6
Place of publication Bethesda USA
Publisher Amer Soc Biochemistry Molecular Biology Inc.
Collection year 2001
Language eng
Subject C1
320305 Medical Biochemistry - Proteins and Peptides
730215 Nutrition
Abstract Genistein is an isoflavenoid that is abundant in soy beans. Genistein has been reported to have a wide range of biological activities and to play a role in the diminished incidence of breast cancer in populations that consume a soy-rich diet. Genistein was originally identified as an inhibitor of tyrosine kinases; however, it also inhibits topoisomerase II by stabilizing the covalent DNA cleavage complex, an event predicted to cause DNA damage. The topoisomerase II inhibitor etoposide acts in a similar manner. Here we show that genistein induces the up-regulation of p53 protein, phosphorylation of p53 at serine 15, activation of the sequence-specific DNA binding properties of p53, and phosphorylation of the hCds1/Chk2 protein kinase at threonine 68. Phosphorylation and activation of p53 and phosphorylation of Chk2 were not observed in ATM-deficient cells. In contrast, the topoisomerase II inhibitor etoposide induced phosphorylation of p53 and Chk2 in ATM-positive and ATM-deficient cells. In addition, genistein-treated ATM-deficient cells were significantly more susceptible to genistein-induced killing than were ATM-positive cells. Together our data suggest that ATM is required for activation of a DNA damage-induced pathway that activates p53 and Chk2 in response to genistein.
Keyword Biochemistry & Molecular Biology
Ataxia-telangiectasia Gene
Dna-damage Checkpoint
Breast-cancer Cells
Protein-kinase
Tyrosine Kinase
Ionizing-radiation
Catalytic Subunit
Topoisomerase-ii
In-vitro
C-abl
Q-Index Code C1

Document type: Journal Article
Sub-type: Article (original research)
Collection: School of Medicine Publications
 
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Created: Wed, 15 Aug 2007, 01:52:46 EST