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 dis ease characterized by immunological, neurological, and developmental d efects 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 molec ular basis of the defect is unknown. A candidate AT gene (ATDC) was is olated on the basis of its ability to complement the ionizing radiatio n sensitivity of AT group D fibroblasts. Whether ATDC is mutated in an y AT patients is not known. We have found that the ATDC protein physic ally 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 an alysis of cultured cells transfected with a plasmid encoding an epitop e-tagged ATDC protein localizes the protein to vimentin filaments. We suggest that the ATDC and hPKCI-1 proteins may be components of a sign al transduction pathway that is induced by ionizing radiation and medi ated by protein kinase C.