The product of the ataxia-telangiectasia group D complementing gene, ATDC, interacts with a protein kinase C substrate and inhibitor.
Ataxia-telangiectasia (AT) is an autosomal recessive human genetic disease characterized by immunological, neurological, and developmental defects and an increased risk of cancer. Cells from individuals with AT show sensitivity to ionizing radiation, elevated recombination, cell cycle abnormalities, and aberrant cytoskeletal organization. The molecular basis of the defect is unknown. A candidate AT gene (ATDC) was isolated on the basis of its ability to complement the ionizing radiation sensitivity of AT group D fibroblasts. Whether ATDC is mutated in any AT patients is not known. We have found that the ATDC protein physically interacts with the intermediate-filament protein vimentin, which is a protein kinase C substrate and colocalizing protein, and with an inhibitor of protein kinase C, hPKCI-1. Indirect immunofluorescence analysis of cultured cells transfected with a plasmid encoding an epitope-tagged ATDC protein localizes the protein to vimentin filaments. We suggest that the ATDC and hPKCI-1 proteins may be components of a signal transduction pathway that is induced by ionizing radiation and mediated by protein kinase C.
Brzoska
P M
PM
Department of Radiation Oncology, University of California, San Francisco 94143-0806, USA.
Chen
H
H
Zhu
Y
Y
Levin
N A
NA
Disatnik
M H
MH
Mochly-Rosen
D
D
Murnane
J P
JP
Christman
M F
MF
D000595:Amino Acid Sequence; D000818:Animals; D001260:Ataxia Telangiectasia / Q000235:genetics* / Q000378:metabolism; D001665:Binding Sites; D001943:Breast Neoplasms; D002417:Cattle; D002460:Cell Line; D002461:Cell Line, Transformed; D002478:Cells, Cultured; D002846:Chromatography, Affinity; D004268:DNA-Binding Proteins / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism*; D005347:Fibroblasts / Q000378:metabolism / Q000528:radiation effects; D005816:Genetic Complementation Test; D006801:Humans; D016350:Leucine Zippers; D008969:Molecular Sequence Data; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000378:metabolism*; D011839:Radiation, Ionizing; D017386:Sequence Homology, Amino Acid; D014157:Transcription Factors; D014407:Tumor Cells, Cultured; D014746:Vimentin / Q000737:chemistry / Q000378:metabolism*; D016335:Zinc Fingers
D004268:DNA-Binding Proteins; C087296:TRIM29 protein, human; D014157:Transcription Factors; D014746:Vimentin; D011493:Protein Kinase C