EDD mediates DNA damage-induced activation of CHK2

Henderson, M. J., Munoz, M. A., Saunders, D. N., Clancy, J. L., Russell, A. J., Williams, B., Pappin, D., Khanna, K. K., Jackson, S. P., Sutherland, R. L., Watts, C. K. (December 2006) EDD mediates DNA damage-induced activation of CHK2. J Biol Chem, 281 (52). pp. 39990-40000. ISSN 0021-9258 (Print)0021-9258 (Linking)

URL: http://www.ncbi.nlm.nih.gov/pubmed/17074762
DOI: 10.1074/jbc.M602818200

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.

Item Type: Paper
Uncontrolled Keywords: Cell Line Cell Line, Tumor DNA Damage/ physiology Enzyme Activation/genetics HeLa Cells Humans Protein Binding/genetics Protein-Serine-Threonine Kinases/ metabolism Signal Transduction/genetics Ubiquitin-Protein Ligases/metabolism/ physiology
Subjects: diseases & disorders > cancer
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification
diseases & disorders
bioinformatics > genomics and proteomics > genetics & nucleic acid processing
Investigative techniques and equipment
Investigative techniques and equipment > RNAI
CSHL Authors:
Communities: CSHL labs > Pappin lab
Depositing User: Matt Covey
Date: 29 December 2006
Date Deposited: 01 Mar 2013 17:30
Last Modified: 01 Mar 2013 17:30
Related URLs:
URI: http://repository.cshl.edu/id/eprint/27661

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