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General Information
Name
hematologic cancer, CUX-related
FlyBase ID
FBhh0000802
Disease Ontology Term
Parent Disease
OMIM
Overview

Haploinsufficiency or inactivating mutations of the human CUX1 gene have been associated with poor prognosis in a number of cancers, including myeloid malignancies. CUX1 belongs to a family of homeodomain-containing transcriptional regulators. There is a single ortholog of CUX1 in Drosophila, Dmel\ct, for which an extensive collection of classical loss-of-function mutations, RNAi-targeting constructs, and alleles caused by insertional mutagenesis have been generated. Dmel\ct is also orthologous to a second human gene, CUX2.

The human Hsap\CUX1 has been introduced into flies, but has not been characterized in the context of this disease model. Heterologous rescue (functional complementation) of the ct wing phenotype is observed.

The identification of human CUX1 among several candidate genes within a haploinsufficient region associated with cancer progression was supported by data from Drosophila, using loss-of-function mutations of Dmel\ct. The hematopoietic system in Drosophila is composed of hemocytes with functions similar to human myeloid cells; haploinsufficiency of ct leads to hemocyte overproliferation and melanotic tumor formation. Many physical and genetic interactions of Dmel\ct have been described, see below and in the ct gene report.

[updated May 2018 by FlyBase; FBrf0222196]

Disease Summary Information
Disease Summary: hematologic cancer, CUX-related
OMIM report
Human gene(s) implicated
Symptoms and phenotype
Genetics
Cellular phenotype and pathology
Molecular information

The protein encoded by CUX1 is a member of the homeodomain family of DNA-binding proteins that appears to play a broad role in mammalian development as a transcriptional repressor of developmentally regulated gene expression. [Gene Cards, CUX1; 2018.05.08]

Work in Drosophila has led to the hypothesis that Cut transcription factors are involved in the coupling of differentiation and apoptosis, a cancer prevention mechanism resulting in the elimination of cells unable to differentiate (Zhai et al., 2012; FBrf0217859).

External links
Disease synonyms
myeloid neoplasm
myeloid tumor
Search term: acute myeloid leukemia
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; the second human gene is CUX1.

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

Many to one: 2 human to 1 Drosophila; the second human gene is CUX2.

Other mammalian ortholog(s) used
    D. melanogaster Gene Information (1)
    Gene Snapshot
    cut (ct) encodes a homeoprotein that functions as a transcriptional factor in many different cells such as wing disc, muscle, oocyte and sense organ cells. It is a regulator of type-specific neuronal identity in the peripheral nervous system. ct is expressed at variable levels in the dendritic arborization (DA) neurons and these levels control the different dendritic morphologies specific for each class of DA neurons. [Date last reviewed: 2019-03-07]
    Cellular component (GO)
    Gene Groups / Pathways
    Comments on ortholog(s)

    Moderate-scoring ortholog of human CUX1 and CUX2; Dmel\ct shares 22% identity and 32-36% 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 (19 groups)
    protein-protein
    Interacting group
    Assay
    References
    anti tag coimmunoprecipitation, peptide massfingerprinting
    anti tag coimmunoprecipitation, peptide massfingerprinting, experimental knowledge based
    anti tag coimmunoprecipitation, peptide massfingerprinting, experimental knowledge based
    anti tag coimmunoprecipitation, peptide massfingerprinting, experimental knowledge based
    anti tag coimmunoprecipitation, peptide massfingerprinting, experimental knowledge based
    anti tag coimmunoprecipitation, peptide massfingerprinting, experimental knowledge based
    anti tag coimmunoprecipitation, peptide massfingerprinting, experimental knowledge based
    two hybrid array
    anti tag coimmunoprecipitation, peptide massfingerprinting, experimental knowledge based
    anti tag coimmunoprecipitation, peptide massfingerprinting, experimental knowledge based
    two hybrid array
    anti tag coimmunoprecipitation, peptide massfingerprinting, experimental knowledge based
    RNA-protein
    Interacting group
    Assay
    References
    pull down, quantitative reverse transcription pcr
    Alleles Reported to Model Human Disease (Disease Ontology) (3 alleles)
    Models Based on Experimental Evidence ( 3 )
    Modifiers Based on Experimental Evidence ( 0 )
    Allele
    Disease
    Interaction
    References
    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
    diepoxybutane
    loss of function allele
    X ray
    References (7)