Human Disease Model Report: cancer, epithelial, ABL-related

General Information

Name

cancer, epithelial, ABL-related

FlyBase ID

FBhh0001070

Disease Ontology Term

carcinoma

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; MIM:189980; MIM: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 MIM:189980, MIM:164690; 2019.07.06]

(OMIM, 2013-)

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]

(FlyBase Curators, 2013-)

External links

Gene2Function (human gene): ABL1
Gene2Function (human gene): ABL2
Gene Cards: ABL1
Gene Cards: ABL2
MedlinePlus (gene): ABL1
MedlinePlus (gene): ABL2
KEGG Disease Pathways: Pathways in Cancer
MARRVEL (human gene): ABL1
MARRVEL (human gene): ABL2
NCBI (Entrez) gene: ABL1; ABL proto-oncogene 1, non-receptor tyrosine kinase
NCBI (Entrez) gene: ABL2; ABL proto-oncogene 2, non-receptor tyrosine kinase

Disease synonyms

Related Diseases

Related human health report(s)

chronic myeloid leukemia, BCR-ABL1 fusions

Ortholog Information

Human gene(s) in FlyBase

Human gene (HGNC)

Symbol / Name

ABL2; ABL proto-oncogene 2, non-receptor tyrosine kinase

D. melanogaster ortholog (based on DIOPT)

Dmel\Abl

(DIOPT, 2013-)

Comments on ortholog(s)

Many to one: 2 human to 1 Drosophila.

Human gene (HGNC)

Symbol / Name

ABL1; ABL proto-oncogene 1, non-receptor tyrosine kinase

D. melanogaster ortholog (based on DIOPT)

Dmel\Abl

(DIOPT, 2013-)

Comments on ortholog(s)

Many to one: 2 human to 1 Drosophila.

Other mammalian ortholog(s) used

D. melanogaster Gene Information (1)

Dmel\Abl

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]

Molecular function (GO)

Cellular component (GO)

Gene Groups / Pathways

NON-RTK

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

H. sapiens (Human)

Other Genes Used: Viral, Bacterial, Synthetic (0)

Summary of Physical Interactions (22 groups)

Abl

protein-protein

Interacting group

Assay

References

Abl

protein kinase assay, autoradiography, enzymatic study

(Lin et al., 2004, Gertler et al., 1995)

Abl - Abi

enzymatic study, western blot, inferred by author, pull down

(Lin et al., 2004, Juang and Hoffmann, 1999)

Abl - capt

anti bait coimmunoprecipitation, anti tag western blot, western blot

(Wills et al., 2002)

Abl - Cdk1

protein kinase assay, autoradiography

(Lin et al., 2004)

Abl - Cyfip

pull down, Identification by mass spectrometry

(Cheong et al., 2020)

Abl - Dab

anti bait coimmunoprecipitation, western blot

(Kannan et al., 2017)

Abl - Dscam1

anti tag coimmunoprecipitation, anti tag western blot

(Sterne et al., 2015)

Abl - dsh

pull down, autoradiography, anti tag coimmunoprecipitation, anti tag western blot, enzymatic study

(Singh et al., 2010)

Abl - Egfr

two hybrid

(Bianco et al., 2007)

Abl - ena

enzymatic study, autoradiography, pull down, western blot, far western blotting, anti tag western blot, peptide massfingerprinting

(Ahern-Djamali et al., 1999, Wills et al., 1999, Ahern-Djamali et al., 1998, Comer et al., 1998, Gertler et al., 1995)

Abl - eya

protein kinase assay, autoradiography

(Xiong et al., 2009)

Abl - fra

pull down, anti tag western blot, anti tag coimmunoprecipitation, western blot

(O'Donnell and Bashaw, 2013, Dorsten et al., 2010, Forsthoefel et al., 2005)

Abl - Hem

pull down, Identification by mass spectrometry

(Cheong et al., 2020)

Abl - Lar

enzymatic study, pull down, autoradiography, western blot, surface plasmon resonance

(Madan et al., 2011, Wills et al., 1999)

Abl - Mical

pull down, anti tag western blot, two hybrid, anti tag coimmunoprecipitation, western blot

(Yoon et al., 2017)

Abl - N

anti bait coimmunoprecipitation, western blot

(Koca et al., 2022)

Abl - Ptp61F

anti tag coimmunoprecipitation, anti tag western blot

(Ku et al., 2009)

Abl - Ptp69D

enzymatic study, autoradiography

(Wills et al., 1999)

Abl - Ptp99A

enzymatic study, surface plasmon resonance

(Madan et al., 2011)

Abl - Pvr

two hybrid

(Bianco et al., 2007)

Abl - robo1

pull down, autoradiography, anti tag coimmunoprecipitation, anti tag western blot, western blot

(O'Donnell and Bashaw, 2013, Bashaw et al., 2000)

Abl - trio

pull down, anti tag western blot

(Forsthoefel et al., 2005)

Alleles Reported to Model Human Disease (Disease Ontology) (4 alleles)

Abl

Models Based on Experimental Evidence ( 0 )

Allele

Disease

Evidence

References

Modifiers Based on Experimental Evidence ( 4 )

Allele

Disease

Interaction

References

Abl^GD1344

ameliorates chronic myeloid leukemia

modeled by Hsap\ABL1::Hsap\BCR^UAS.cBa

(Bernardoni et al., 2019)

Abl¹

ameliorates fragile X syndrome

modeled by Fmr1^Δ50M

(Sterne et al., 2015)

Abl^K417N.UAS

ameliorates chronic myeloid leukemia

modeled by Hsap\ABL1::Hsap\BCR^UAS.cBa

(Bernardoni et al., 2019)

Abl^UAS.cFa

exacerbates chronic myeloid leukemia

modeled by Hsap\ABL1::Hsap\BCR^UAS.cBa

(Bernardoni et al., 2019)

ameliorates Huntington's disease

modeled by Hsap\HTT^{128Q.1-231.UAS}

(Onur et al., 2021)

Alleles Representing Disease-Implicated Variants

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

Related mammalian, viral, bacterial, or synthetic transgenes

Allele

Transgene

Publicly Available Stocks

Hsap\ABL2^UAS.cBa

PBac{UAS-hABL2.B}

y¹ w^*; PBac{UAS-hABL2.B}VK00037

Hsap\ABL2^A1084T.UAS

PBac{UAS-hABL2.A1084T}

y¹ w^*; PBac{UAS-hABL2.A1084T}VK00037

Selected Drosophila transgenes

Allele

Transgene

Publicly Available Stocks

Abl^UAS.cFa

P{UAS-Abl.F}

w^*; P{UAS-Abl.F}2/CyO; TM2/TM6B, Tb¹

Abl^K417N.UAS

P{UAS-Abl.K417N}

P{UAS-Abl.K417N}2; Abl¹ e^*/TM6B, Tb¹

RNAi constructs available

Allele

Transgene

Publicly Available Stocks

y¹ v¹; P{TRiP.JF02960}attP2

y¹ sc^* v¹ sev²¹; P{TRiP.GL00234}attP2

y¹ sc^* v¹ sev²¹; P{TRiP.HMC05140}attP40

Selected Drosophila classical alleles

Allele

Allele class

Mutagen

Publicly Available Stocks

Abl^KO

amorphic allele - molecular evidence

CRISPR/Cas9

w^*; Abl^KO/TM3, Sb¹

Abl²

amorphic allele - genetic evidence

Abl²/TM6B, Tb¹

Abl¹

Abl¹ kar¹ red¹ e¹/TM6B, Tb¹

References (5)

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