Altered protein synthesis in ataxia--telangiectasia fibroblasts

Analysis of protein production in various strains of ataxia--telangiectasia (A--T) fibroblasts demonstrated the overproduction of a group of secreted proteins and variations in the protein characteristics of the extracellular matrix. The most prominent differences involved fibronectin, which was identified by immunochemical analysis. One- and two-dimensional gel electrophoresis demonstrated differences in the production, accumulation, and molecular weight of fibronectin on the cell surface and in the culture medium as compared to normal human fibroblasts. Three other secreted proteins with molecular weights of 185 000, 150 000, and 70 000 were also observed to be produced in excess amounts in some strains of A-T. The finding that extracellular matrix alterations are involved in the abnormal DNA synthesis and reduced cell survival in A-T cells in response to X radiation would be additional evidence for a close association between the extracellular and nuclear architecture.