ABL (gene)

Human gene encoding a protein-tyrosine kinase

Overview

The ABL gene encodes a protein known as the Abelson murine leukemia viral oncogene homolog 1, or ABL1. This protein is a member of the tyrosine kinase family and plays a crucial role in various cellular processes, including cell division, adhesion, and stress response. The ABL gene is located on chromosome 9 in humans.

Structure

The ABL1 protein consists of several domains that contribute to its function. These include the SH3 domain, SH2 domain, and a tyrosine kinase domain. The SH3 and SH2 domains are involved in protein-protein interactions, while the tyrosine kinase domain is responsible for its enzymatic activity.

Function

The ABL1 protein is involved in the regulation of the cytoskeleton, which is essential for cell shape and movement. It also plays a role in the DNA damage response and can influence apoptosis, or programmed cell death. ABL1 is activated in response to various cellular signals and can translocate to different cellular compartments, including the nucleus.

Clinical significance

Mutations or translocations involving the ABL gene can lead to the development of certain types of cancer. One of the most well-known translocations is the Philadelphia chromosome, which results from a translocation between chromosomes 9 and 22. This translocation creates the BCR-ABL fusion protein, which is associated with chronic myeloid leukemia (CML).

Inhibitors

Several tyrosine kinase inhibitors (TKIs) have been developed to target the BCR-ABL fusion protein in CML. These include imatinib, dasatinib, and nilotinib. These drugs have significantly improved the prognosis for patients with CML by specifically inhibiting the aberrant kinase activity of the BCR-ABL protein.

Research

Ongoing research is focused on understanding the full range of ABL1's functions in normal and cancerous cells. Studies are also exploring resistance mechanisms to TKIs and developing new therapeutic strategies to overcome these challenges.

Related pages

• Tyrosine kinase
• Chronic myeloid leukemia
• Philadelphia chromosome
• BCR-ABL fusion protein

Gallery

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  Structure of Abl1 bound to nilotinib