ABL (gene)

Abelson murine leukemia viral oncogene homolog 1 also known as ABL1 is a is_associated_with::protein that, in humans, is encoded by the ABL1 is_associated_with::gene (previous symbol ABL) located on is_associated_with::chromosome 9. 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.

Function
The ABL1 proto-oncogene encodes a cytoplasmic and nuclear protein is_associated_with::tyrosine kinase that has been implicated in processes of cell differentiation, is_associated_with::cell division, is_associated_with::cell adhesion, and stress response. Activity of ABL1 protein is negatively regulated by its is_associated_with::SH3 domain, and deletion of the SH3 domain turns ABL1 into an is_associated_with::oncogene. The t(9;22) translocation results in the head-to-tail fusion of the BCR and ABL1 genes, leading to a is_associated_with::fusion gene present in many cases of chronic is_associated_with::myelogenous leukemia. The DNA-binding activity of the ubiquitously expressed ABL1 tyrosine kinase is regulated by is_associated_with::CDC2-mediated is_associated_with::phosphorylation, suggesting a cell cycle function for ABL1. The ABL1 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.

Clinical significance
Mutations in the ABL1 gene are associated with is_associated_with::chronic myelogenous leukemia (CML). In CML, the gene is activated by being translocated within the BCR (breakpoint cluster region) is_associated_with::gene on chromosome 22. This new is_associated_with::fusion gene, BCR-ABL, encodes an unregulated, cytoplasm-targeted tyrosine kinase that allows the cells to proliferate without being regulated by is_associated_with::cytokines. This, in turn, allows the cell to become is_associated_with::cancerous.

This gene is a partner in a is_associated_with::fusion gene with the BCR gene in the is_associated_with::Philadelphia chromosome, a characteristic abnormality in chronic is_associated_with::myelogenous leukemia (CML) and rarely in some other is_associated_with::leukemia forms. The BCR-ABL transcript encodes a is_associated_with::tyrosine kinase, which activates mediators of the is_associated_with::cell cycle regulation system, leading to a clonal is_associated_with::myeloproliferative disorder. The BCR-ABL protein can be inhibited by various small molecules. One such inhibitor is imatinib mesylate, which occupies the tyrosine kinase domain and inhibits BCR-ABL's influence on the is_associated_with::cell cycle. Second generation BCR-ABL tyrosine-kinase inhibitors are also under development to inhibit BCR-ABL mutants resistant to imatinib.

Interactions
Abl gene has been shown to interact with:


 * is_associated_with::ABI1,
 * is_associated_with::ABI2,
 * is_associated_with::ABL2,
 * ATM,
 * is_associated_with::BCAR1,
 * BCR,
 * is_associated_with::BRCA1,
 * CAT,
 * CBL,
 * is_associated_with::CRKL,
 * is_associated_with::DOK1,
 * EPHB2,
 * is_associated_with::GPX1,
 * is_associated_with::GRB10,
 * MTOR,
 * is_associated_with::GRB2,
 * MDM2,
 * is_associated_with::NCK1,
 * is_associated_with::NEDD9,
 * NTRK1,
 * is_associated_with::P73,
 * is_associated_with::PAG1,
 * is_associated_with::PAK2,
 * is_associated_with::PSTPIP1,
 * is_associated_with::RAD9A,
 * is_associated_with::RAD51,
 * RB1,
 * is_associated_with::RFX1,
 * is_associated_with::RYBP,
 * is_associated_with::SHC1,
 * is_associated_with::SORBS2,
 * SPTA1,
 * is_associated_with::SPTAN1,
 * is_associated_with::TERF1,
 * is_associated_with::VAV1, and
 * is_associated_with::YTHDC1.

Regulation
There is some evidence that the expression of Abl is regulated by the microRNA miR-203.