title: c-Abl in oxidative stress, aging and cancer.
abstract: 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.
authors.affiliation: The Institute of Molecular and Cell Biology, Proteos, Singapore. libj@imcb.a-star.edu.sg
authors.forename: Baojie
authors.initials: B
authors.lastname: Li
mesh_terms: D000375:Aging / Q000502:physiology*; D000818:Animals; D064007:Ataxia Telangiectasia Mutated Proteins; D018797:Cell Cycle Proteins / Q000235:genetics / Q000502:physiology; D004268:DNA-Binding Proteins / Q000235:genetics / Q000502:physiology; D016044:Fusion Proteins, bcr-abl / Q000235:genetics / Q000502:physiology; D005786:Gene Expression Regulation / Q000502:physiology; D015972:Gene Expression Regulation, Neoplastic; D016313:Genes, abl; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000209:etiology / Q000503:physiopathology; D051379:Mice; D009369:Neoplasms / Q000235:genetics / Q000503:physiopathology*; D016374:Oncogene Proteins v-abl / Q000235:genetics / Q000502:physiology; D018384:Oxidative Stress / Q000502:physiology*; D010544:Peroxidases / Q000235:genetics / Q000502:physiology; D054464:Peroxiredoxins; D051745:Protein Kinase C-delta / Q000502:physiology; D011499:Protein Processing, Post-Translational; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000502:physiology; D016315:Proto-Oncogene Proteins c-abl / Q000235:genetics / Q000502:physiology*; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000502:physiology
chemical_list: D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D016374:Oncogene Proteins v-abl; D025521:Tumor Suppressor Proteins; D010544:Peroxidases; D054464:Peroxiredoxins; D016044:Fusion Proteins, bcr-abl; D016315:Proto-Oncogene Proteins c-abl; C576324:ATM protein, human; D064007:Ataxia Telangiectasia Mutated Proteins; C576325:Atm protein, mouse; D017346:Protein Serine-Threonine Kinases; D051745:Protein Kinase C-delta