EDD mediates DNA damage-induced activation of CHK2

Henderson, Michelle J., Munoz, Marcia A, Saunders, Darren N., Clancy, Jennifer L., Russell, Amanda J., Williams, Brandi, Pappin, Darryl, Khanna, Kum Kum, Jackson, Stephen P., Sutherland, Robert L. and Watts, Colin K. W. (2006) EDD mediates DNA damage-induced activation of CHK2. Journal of Biological Chemistry, 281 52: 39990-40000. doi:10.1074/jbc.M602818200

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Author Henderson, Michelle J.
Munoz, Marcia A
Saunders, Darren N.
Clancy, Jennifer L.
Russell, Amanda J.
Williams, Brandi
Pappin, Darryl
Khanna, Kum Kum
Jackson, Stephen P.
Sutherland, Robert L.
Watts, Colin K. W.
Title EDD mediates DNA damage-induced activation of CHK2
Journal name Journal of Biological Chemistry   Check publisher's open access policy
ISSN 0021-9258
Publication date 2006-10
Sub-type Article (original research)
DOI 10.1074/jbc.M602818200
Open Access Status File (Publisher version)
Volume 281
Issue 52
Start page 39990
End page 40000
Total pages 11
Place of publication Bethesda, MD, U.S.
Publisher American Society for Biochemistry and Molecular Biology
Language eng
Subject 06 Biological Sciences
0601 Biochemistry and Cell Biology
Abstract EDD, the human orthologue of Drosophila melanogaster “hyperplastic discs,” is overexpressed or mutated in a number of common human cancers. Although EDD has been implicated in DNA damage signaling, a definitive role has yet to be demonstrated. Here we report a novel interaction between EDD and the DNA damage checkpoint kinase CHK2. EDD and CHK2 associate through a phospho-dependent interaction involving the CHK2 Forkhead-associated domain and a region of EDD spanning a number of putative Forkhead-associated domain-binding threonines. Using RNA interference, we demonstrate a critical role for EDD upstream of CHK2 in the DNA damage signaling pathway. EDD is necessary for the efficient activating phosphorylation of CHK2 in response to DNA damage following exposure to ionizing radiation or the radiomimetic, phleomycin. Cells depleted of EDD display impaired CHK2 kinase activity and an inability to respond to DNA damage. These results identify EDD as a novel mediator in DNA damage signal transduction via CHK2 and emphasize the potential importance of EDD in cancer.
Keyword DNA damage
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Non-UQ

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 35 times in Thomson Reuters Web of Science Article | Citations
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Created: Fri, 15 Jan 2010, 13:32:25 EST by Ms May Balasaize on behalf of Faculty Of Health Sciences