cAbl

cAbl, or cellular Abelson murine leukemia virus oncogene homolog 1, is a non-receptor protein tyrosine kinase of the Abl family encoded by the human ABL1 gene. It participates in signal transduction pathways that regulate cell growth, differentiation, adhesion, and the cellular response to DNA damage. The protein features an N-terminal myristoylation site and regulatory regions including SH3 and SH2 domains, a central tyrosine kinase catalytic domain, and a C-terminal region involved in actin cytoskeleton regulation. This architecture allows cAbl to shuttle between the cytoplasm and nucleus, and its activity is normally restrained by intramolecular interactions and autoinhibition that involve the myristoylation and SH3/SH2 module.

Functions of cAbl include regulation of cytoskeletal dynamics and cell migration through substrates involved in actin remodeling, and participation in the DNA damage response, where p73-dependent apoptosis can be promoted. In response to cellular stress or growth factor signals, cAbl can be activated and may translocate to the nucleus or engage in cytoplasmic signaling networks.

Pathology and clinical relevance: Aberrant activation of Abl family kinases is linked to cancer. The BCR-ABL fusion, resulting from the Philadelphia chromosome translocation t(9;22), yields a constitutively active oncoprotein that drives chronic myeloid leukemia and, in some cases, acute lymphoblastic leukemia. Targeted inhibitors of Abl kinase, including imatinib and other tyrosine kinase inhibitors, have substantially improved treatment outcomes, though resistance can arise via kinase-domain mutations or alternative signaling pathways. cAbl remains a central component of cellular signaling networks and a focus of ongoing research.