Proto-oncogene tyrosine-protein kinase Abl1 (ABL1)

Proto-oncogene tyrosine-protein kinase Abl1 (ABL1) is a non-receptor tyrosine kinase encoded by the ABL1 gene on chromosome 9.[4][5][7] It plays a central role in signal transduction pathways controlling cell growth, survival, cytoskeleton remodeling, and response to DNA damage.[3][4] ABL1 contains modular domains including SH2 and SH3, which regulate its kinase activity through autoinhibition and subcellular localization. In normal physiology, ABL1 shuttles between cytoplasm and nucleus and participates in DNA repair and cell migration. The chromosomal translocation t(9;22) creates the BCR-ABL1 fusion gene, resulting in constitutive kinase activation, which drives the development of chronic myeloid leukemia and other cancers.[5][6][7][1] Targeted inhibition of ABL1 activity by small-molecule tyrosine kinase inhibitors (TKIs) such as imatinib has revolutionized the treatment of Philadelphia chromosome–positive leukemias, though the emergence of resistance mutations such as T315I is a significant clinical challenge.[6][8][7]

Other names

Abelson murine leukemia viral oncogene homolog 1Abelson tyrosine-protein kinase 1Proto-oncogene c-Ablp150JTK7Tyrosine-protein kinase ABL1ABL

Inhibition of ATP-binding site (competitive kinase inhibition) Allosteric inhibition Irreversible and reversible covalent inhibition of catalytic lysine