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General Information
Name
cancer, epithelial, ABL-related
FlyBase ID
FBhh0001070
Disease Ontology Term
Parent Disease
OMIM
Overview

Both ABL1 and ABL2 are associated with leukemias as components of oncogenic translocations (see human disease model report 'chronic myeloid leukemia, BCR-ABL1 fusions' FBhh0001049; OMIM:189980; OMIM:164690). This report describes characterization of the role of Abelson kinase in a different oncogenic context: epithelial cells. The Drosophila ortholog of ABL1 and ABL2, Dmel\Abl, has been used; classical amorphic and hypomorphic alleles, RNAi-targeting constructs, and alleles caused by insertional mutagenesis have been generated for Dmel\Abl.

The human genes Hsap\ABL1 and Hsap\ABL2 have been introduced into flies, but have not been characterized in the context of this disease model.

Overexpression of Dmel\Abl in the wing disc causes loss of epithelial apical/basal cell polarity and secretion of matrix metalloproteinases, resulting in cell invasion and overproliferation. Increased cell proliferation associated with ABL can be separated from its cell invasion function by distinct downstream effectors. Evidence of an ABL/SRC signal amplification loop in epithelial cell invasion has been described and the clinical relevance of this observation noted.

[updated Jul. 2019 by FlyBase; FBrf0222196

Disease Summary Information
Disease Summary: cancer, epithelial, ABL-related
OMIM report
Human gene(s) implicated
Symptoms and phenotype
Genetics

Both ABL1 and ABL2 are associated with leukemias as members of oncogenic translocations. [from OMIM:189980, OMIM:164690; 2019.07.06]

Cellular phenotype and pathology
Molecular information

ABL1 and ABL2 encode members of the Abelson family of nonreceptor tyrosine protein kinases. The genes play overlapping roles in key processes linked to cell growth, morphogenesis and survival such as cytoskeleton remodeling in response to extracellular stimuli, cell motility and adhesion, receptor endocytosis, autophagy, DNA damage response and apoptosis. They coordinate actin remodeling through tyrosine phosphorylation of proteins controlling cytoskeleton dynamics. [Gene Cards, ABL1, ABL2; 2019.07.05]

External links
Disease synonyms
Ortholog Information
Human gene(s) in FlyBase
Human gene (HGNC)
D. melanogaster ortholog (based on DIOPT)
Comments on ortholog(s)

Many to one: 2 human to 1 Drosophila.

Human gene (HGNC)
D. melanogaster ortholog (based on DIOPT)
Comments on ortholog(s)

Many to one: 2 human to 1 Drosophila.

Other mammalian ortholog(s) used
    D. melanogaster Gene Information (1)
    Gene Snapshot
    Abl tyrosine kinase (Abl) encodes a non-receptor tyrosine kinase best known for its ortholog's role in human leukemia. It phosphorylates cell adhesion and cytoskeletal proteins and acts as a scaffold in a signaling complex to regulate both epithelial and nervous system morphogenesis. [Date last reviewed: 2019-03-07]
    Gene Groups / Pathways
    Comments on ortholog(s)

    Moderate-scoring ortholog of human ABL1 and ABL2 (1 Drosophila to 2 human). Dmel\Abl shares 33-38% identity and 42-48% similarity with the human genes.

    Orthologs and Alignments from DRSC
    DIOPT - DRSC Integrative Ortholog Prediction Tool - Click the link below to search for orthologs in Humans
    Synthetic Gene(s) Used (0)
    Summary of Physical Interactions (21 groups)
    protein-protein
    Interacting group
    Assay
    References
    protein kinase assay, autoradiography, enzymatic study
    enzymatic study, western blot, inferred by author, pull down
    anti bait coimmunoprecipitation, anti tag western blot, western blot
    protein kinase assay, autoradiography
    pull down, Identification by mass spectrometry
    anti bait coimmunoprecipitation, western blot
    anti tag coimmunoprecipitation, anti tag western blot
    enzymatic study, autoradiography, anti tag coimmunoprecipitation, anti tag western blot, pull down
    enzymatic study, autoradiography, pull down, western blot, far western blotting, anti tag western blot, peptide massfingerprinting
    protein kinase assay, autoradiography
    anti tag coimmunoprecipitation, anti tag western blot, western blot, pull down
    pull down, Identification by mass spectrometry
    enzymatic study, autoradiography, pull down, western blot, surface plasmon resonance
    anti tag coimmunoprecipitation, western blot, pull down, anti tag western blot, two hybrid
    anti tag coimmunoprecipitation, anti tag western blot
    enzymatic study, autoradiography
    enzymatic study, surface plasmon resonance
    pull down, autoradiography, anti tag coimmunoprecipitation, anti tag western blot, western blot
    pull down, anti tag western blot
    Alleles Reported to Model Human Disease (Disease Ontology) (4 alleles)
    Models Based on Experimental Evidence ( 0 )
    Allele
    Disease
    Evidence
    References
    Modifiers Based on Experimental Evidence ( 4 )
    Genetic Tools, Stocks and Reagents
    Sources of Stocks
    Contact lab of origin for a reagent not available from a public stock center.
    Bloomington Stock Center Disease Page
    Selected mammalian transgenes
    Allele
    Transgene
    Publicly Available Stocks
    Selected Drosophila transgenes
    Allele
    Transgene
    Publicly Available Stocks
    RNAi constructs available
    Allele
    Transgene
    Publicly Available Stocks
    Selected Drosophila classical alleles
    Allele
    Allele class
    Mutagen
    Publicly Available Stocks
    amorphic allele - genetic evidence
    References (5)