c-Abl in oxidative stress, aging and cancer

c-Abl is activated by oxidative stress but its precise function in cell response to this stress is elusive. Studies of c-Abl(-/-) osteoblasts revealed that c-Abl played a negative role in the induction of peroxiredoxin I (Prx I, Prdx I), an anti-oxidant protein with tumor suppression activity. In contrast, Atm, a signaling molecule that interacts with c-Abl and is required for c-Abl activation, served a totally different function. The significance of these findings is discussed here in the context of aging and tumorigenesis and their links to reactive oxygen species. c-Abl and its derivatives BCR-ABL and v-Abl were discovered more than twenty years ago. BCR-ABL and v-Abl acquire elevated tyrosine kinase activities by fusing to BCR and gag respectively and are capable of transforming myeloid and fibroblast cells. BCR-ABL is also the underlying cause in the development of most cases of chronic myeloid leukemia (CML) in humans. In contrast, c-Abl takes on an auto-inhibiting conformation and its activation requires post-translational modifications such as phosphorylation and myristoylation. The physiological functions of c-Abl remain elusive.