CELL DEATH AND SURVIVAL IN ATAXIA TELANGIECTASIA: ROLE OF THE ATM/ABL PATHWAY

Ataxia telangiectasia (AT) is neuromuscular disease characterized by progressive neurodegeneration leading to ataxia and dilatation of blood vessels in the eye and facial area (telangiectasia). Patients show also high incidence of tumorigenesis in the lymphoid system and deficiency in immunoresponses. The frequency of AT has been estimated around 1:40.000. Unfortunately, no effective tretments have been found yet to alter the course of this disease. The gene responsible for AT has been identified and named ATM (Ataxia Telangiectasia Mutated gene). AT patients are characterized by mutations in this gene, and therefore in the corrisponding protein, that impair its proper function. The aim of this project is to elucidate the mode of action of ATM and to characterize its cellular effectors. The c-Abl protein has been shown to be a physiological substrate of ATM. Cells derived from AT patients show defects also in the Abl signal transduction pathway. Therefore Abl is an important effector of ATM. The characterization of the ATM-Abl signaling and the identification of new factors that execute ATM and Abl function will possibly allow to design therapeutical approaches.