Tyrosine-protein kinase ABL1 also known asABL1 is aprotein that, in humans, is encoded by theABL1gene (previous symbolABL) located onchromosome 9.[5] c-Abl is sometimes used to refer to the version of the gene found within the mammalian genome, while v-Abl refers to the viral gene, which was initially isolated from theAbelson murine leukemia virus.[6]
TheABL1proto-oncogene encodes a cytoplasmic and nuclear proteintyrosine kinase that has been implicated in processes of cell differentiation,cell division,cell adhesion, and stress response such asDNA repair.[7][8][9][10] Activity of ABL1 protein is negatively regulated by itsSH3 domain, and deletion of the SH3 domain turns ABL1 into anoncogene. Thet(9;22) translocation results in the head-to-tailfusion of theBCR andABL1 genes, leading to afusion gene present in many cases of chronicmyelogenous leukemia. The DNA-binding activity of the ubiquitously expressed ABL1 tyrosine kinase is regulated byCDC2-mediatedphosphorylation, suggesting a cell cycle function for ABL1. TheABL1 gene is expressed as either a 6- or a 7-kb mRNA transcript, with alternatively spliced first exons spliced to the common exons 2–11.[11]
Mutations in theABL1 gene are associated withchronic myelogenous leukemia (CML). In CML, the gene is activated by beingtranslocated within the BCR (breakpoint cluster region)gene on chromosome 22. This new fusion gene,BCR-ABL, encodes an unregulated, cytoplasm-targeted tyrosine kinase that allows the cells to proliferate without being regulated bycytokines. This, in turn, allows the cell to becomecancerous.
This gene is a partner in a fusion gene with theBCR gene in thePhiladelphia chromosome, a characteristic abnormality in chronicmyelogenous leukemia (CML) and rarely in some otherleukemia forms. The BCR-ABL transcript encodes atyrosine kinase, which activates mediators of thecell cycle regulation system, leading to a clonalmyeloproliferative disorder. The BCR-ABL protein can be inhibited by various small molecules. One such inhibitor isimatinib mesylate, which occupies the tyrosine kinase domain and inhibits BCR-ABL's influence on thecell cycle. Second generationBCR-ABL tyrosine-kinase inhibitors are also under developmentto inhibit BCR-ABL mutants resistant to imatinib.[12]
ABL gene has been shown tointeract with:
There is some evidence that the expression of Abl is regulated by the microRNAmiR-203.[61]
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