c-Abl (Abelson murine leukemia viral oncogene homolog 1, ABL1) is a 140 kDa proto-oncogene member of the Src family of non-receptor tyrosine kinases. c-Abl has been implicated in processes of cell differentiation, cell division, cell adhesion, and stress response. Activity of c-Abl protein is negatively regulated by its SH3 domain, and deletion of the SH3 domain turns c-Abl into an oncogene. The t(9;22) translocation results in the head-to-tail fusion of the BCR and c-Abl genes present in many cases of chronic myelogeneous leukemia. The DNA-binding activity of the ubiquitously expressed ABL1 tyrosine kinase is regulated by CDC2-mediated phosphorylation, suggesting a cell cycle function for c-Abl. In chronic myelogenous leukemia and a subset of acute lymphoblastic leukemias, the c-Abl proto oncogene undergoes a (9;22) chromosomal translocation producing a novel rearranged chromosome (the Philadelphia chromosome) As the result of the fusion of c-Abl sequences from chromosome 9 to the Bcr gene on chromosome 22. The molecular consequence of this translocation is the generation of a chimeric Bcr/Abl mRNA encoding activated Abl protein tyrosine kinase. The c-Abl oncogene was initially identified as the viral transforming gene of Abelson murine leukemia virus (A-MuLV). The major translational product of c-Abl has been identified as a protein with tyrosine kinase activity and an SH2 domain. The c-Abl oncogene is implicated in several human leukemias including 90-95% of chronic myelocytic leukemia (CML), 20-25% of adult acute lymphoblastic leukemia (ALL) and 2-5% of pediatric ALL. c-Abl localizes to dynamic actin structures, and phosphorylates CRK and CRKL, DOK1, and other proteins controlling cytoskeleton dynamics. c-ABL potentially regulates DNA repair by activating the proapoptotic pathway when the DNA damage is too severe to be repaired.
Abelson murine leukemia viral oncogene homolog 1; Abelson tyrosine-protein kinase 1; Abl 1 antib; ABL2; ABLL; ARG; B30; bcr/c-abl oncogene protein; c-abl oncogene 1, receptor tyrosine kinase; p150; Proto-oncogene c-Abl; proto-oncogene tyrosine-protein kinase ABL1; RP11-83J21.1; Tyrosine kinase ARG; Tyrosine-protein kinase ABL1; v-abl Abelson murine leukemia viral oncogene homolog 1