Induction of colonic epithelial cell apoptosis by p47-dependent oxidants.
Exogenous oxidants appear capable of initiating both proliferative and death signals, but the role of endogenous oxidants in either tumorigenesis or tumor suppression is unclear. We found that expression of the NAD(P)H oxidase adapter p47(phox) was suppressed in human colon carcinoma specimens relative to adjacent normal colon. Overexpression of p47(phox) increased apoptosis in colon cancer cell lines independent of p53 and mismatch-repair competency. p47(phox) was found to interact with the c-Abl adapter Abl interactor-1 (ABI-1), and p47(phox) coprecipitated with both ABI-1 and c-Abl. Ectopic expression of p47(phox) in colon cancer cells increased oxidant production with phosphorylation and activation of nuclear c-Abl and consequent apoptosis. Colonic epithelial p47(phox) may be specifically targeted to a c-Abl-containing complex that serves a physiologic tumor suppressing function.
Gu
Ying
Y
Department of Internal Medicine, University of Texas Southwestern and the Dallas VAMC, Mail Code 151, 4500 S Lancaster Rd, Dallas, TX 75216, USA.
Souza
Rhonda F
RF
Wu
Ru Feng
RF
Xu
You Cheng
YC
Terada
Lance S
LS
D048868:Adaptor Proteins, Signal Transducing; D017209:Apoptosis / Q000502:physiology*; D003110:Colonic Neoplasms / Q000473:pathology*; D003598:Cytoskeletal Proteins; D004847:Epithelial Cells / Q000473:pathology; D018398:Homeodomain Proteins / Q000378:metabolism; D006801:Humans; D008969:Molecular Sequence Data; D019255:NADPH Oxidases; D010750:Phosphoproteins / Q000378:metabolism / Q000502:physiology*; D011233:Precipitin Tests; D011485:Protein Binding; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014407:Tumor Cells, Cultured; D020798:Two-Hybrid System Techniques
C513733:ABI1 protein, human; D048868:Adaptor Proteins, Signal Transducing; D003598:Cytoskeletal Proteins; D018398:Homeodomain Proteins; D010750:Phosphoproteins; D019255:NADPH Oxidases; C060505:neutrophil cytosolic factor 1