Abl gene

V-abl Abelson murine leukemia viral oncogene homolog 1
File:PBB Protein ABL1 image.jpg PDB rendering based on 1ab2.
Available structures PDB Ortholog search: Template:Homologene2PDBe PDBe, Template:Homologene2uniprot RCSB List of PDB id codes 1ab2​, 1abo​, 1abq​, 1awo​, 1bbz​, 1fpu​, 1iep​, 1ju5​, 1m52​, 1opj​, 1opk​, 1opl​, 1zzp​, 2abl​, 2e2b​, 2f4j​, 2fo0​, 2g1t​, 2g2f​, 2g2h​, 2g2i​, 2gqg​, 2hiw​, 2hyy​, 2hz0​, 2hz4​, 2hzi​, 2hzn​, 2o88​
Identifiers
Symbols	ABL1 ; ABL; JTK7; bcr/abl; c-ABL; p150; v-abl
External IDs	Template:OMIM5 Template:MGI HomoloGene: 3783
Gene ontology Molecular function Template:GNF GO Template:GNF GO Template:GNF GO Template:GNF GO Template:GNF GO Template:GNF GO Template:GNF GO Template:GNF GO Template:GNF GO Cellular component Template:GNF GO Template:GNF GO Template:GNF GO Biological process Template:GNF GO Template:GNF GO Template:GNF GO Template:GNF GO Template:GNF GO Template:GNF GO Template:GNF GO Template:GNF GO Template:GNF GO Template:GNF GO
RNA expression pattern
More reference expression data
Orthologs
Template:GNF Ortholog box
Species	Human	Mouse
Entrez	n/a	n/a
Ensembl	n/a	n/a
UniProt	n/a	n/a
RefSeq (mRNA)	n/a	n/a
RefSeq (protein)	n/a	n/a
Location (UCSC)	n/a	n/a
PubMed search	n/a	n/a

The abl gene is associated with chronic myelogenous leukemia. The abl gene is located on the 9th chromosome. This gene is activated by being translocated within the bcr (breakpoint cluster region) gene on chromosome 22. This new abl/bcr (chimeric) gene encodes a tyrosine kinase which allows the cells to proliferate without being regulated by cytokines. This in turn allows the cell to become cancerous.

The ABL1 protooncogene encodes a cytoplasmic and nuclear protein tyrosine kinase that has been implicated in processes of cell differentiation, cell division, cell adhesion, and stress response. Activity of c-Abl protein is negatively regulated by its SH3 domain, and deletion of the SH3 domain turns ABL1 into an oncogene. The t(9;22) translocation results in the head-to-tail fusion of the BCR (MIM:151410) and ABL1 genes present in many cases of chronic myelogeneous leukemia. The DNA-binding activity of the ubiquitously expressed ABL1 tyrosine kinase is regulated by CDC2-mediated phosphorylation, suggesting a cell cycle function for ABL1. The ABL1 gene is expressed as either a 6- or 7-kb mRNA transcript, with alternatively spliced first exons spliced to the common exons 2-11.

This gene is fused with the bcr gene in a Philadelphia chromosome, the characteristic abnormality in chronic myelogenous leukemia (CML) and rarely in some other leukemia forms. The bcr-abl transcript is also a tyrosine kinase, which activates mediators of the cell cycle regulation system, leading to a clonal myeloproliferative disorder. The bcr-abl protein can be inhibited with the agent imatinib mesylate, which occupies the TK domain and inhibits bcr-abls influence on the cell cycle.

Further reading

• Clark, Stevens. "Publications." Research Papers 1986-1989. <http://www.humonc.wisc.edu/clark/publications_abstract1x.html>
• Dunitz, Martin. "Chronic Myeloid Leukaemia" 2001. Taylor & Francis, Limited. Published online via Ebrary.com
• Scott K Shore, Ramana V Tantravahi and E Premkumar Reddy. "Transforming pathways activated by the v-Abl tyrosine kinase" 9 Dec. 2002. <http://www.nature.com/onc/journal/v21/n56/full/1206084a.html>
• Shaul Y (2000). "c-Abl: activation and nuclear targets". Cell Death Differ. 7 (1): 10–6. doi:10.1038/sj.cdd.4400626. PMID 10713716.
• Era T (2002). "Bcr-Abl is a "molecular switch" for the decision for growth and differentiation in hematopoietic stem cells". Int. J. Hematol. 76 (1): 35–43. PMID 12138893.
• Pendergast AM (2003). "The Abl family kinases: mechanisms of regulation and signaling". Adv. Cancer Res. 85: 51–100. PMID 12374288.
• Keung YK, Beaty M, Steward W; et al. (2003). "Chronic myelocytic leukemia with eosinophilia, t(9;12)(q34;p13), and ETV6-ABL gene rearrangement: case report and review of the literature". Cancer Genet. Cytogenet. 138 (2): 139–42. PMID 12505259.CS1 maint: Explicit use of et al. (link) CS1 maint: Multiple names: authors list (link)
• Saglio G, Cilloni D (2005). "Abl: the prototype of oncogenic fusion proteins". Cell. Mol. Life Sci. 61 (23): 2897–911. doi:10.1007/s00018-004-4271-0. PMID 15583852.
• Shaul Y, Ben-Yehoyada M (2005). "Role of c-Abl in the DNA damage stress response". Cell Res. 15 (1): 33–5. doi:10.1038/sj.cr.7290261. PMID 15686624.
• Yoshida K (2007). "Regulation for nuclear targeting of the Abl tyrosine kinase in response to DNA damage". Adv. Exp. Med. Biol. 604: 155–65. PMID 17695727.

See also

• BCR gene

External links

• Genes,+abl at the US National Library of Medicine Medical Subject Headings (MeSH)
• Online Mendelian Inheritance in Man (OMIM) 189980 (ABL)
• Abelson+Leukemia+Virus at the US National Library of Medicine Medical Subject Headings (MeSH)