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General Information
Name
cancer, neural stem cell, TRIM2,3-related
FlyBase ID
FBhh0000772
Disease Ontology Term
Parent Disease
OMIM
Overview

The role of neuroblasts in the development of the Drosophila larval/adult brain has served as a model for the role of adult neural stem cells in normal neural development and in tumor formation. Asymmetric cell division, a critical part of the process of stem cell renewal vs. differentiation, has been extensively studied in the context of this system. Loss-of-function mutations that affect normal neuroblast differentiation in Drosophila often result in conspicuous phenotypes of overproliferation and tumorous expansion of the brain at the larval stage. Based on this phenotype, a number of genes impacting this process in flies have been identified. This report describes a human disease model using the fly gene brat, a negative regulator of translation. In human, there are two genes orthologous to Dmel\brat, TRIM3 and TRIM2, members of the tripartite motif (TRIM) family. Classical amorphic and hypomorphic mutations, RNAi-targeting constructs, and alleles caused by insertional mutagenesis have been generated for Dmel\brat.

Neither human gene, TRIM3 or TRIM2, has been introduced into flies. In humans, there is evidence implicating TRIM3 in malignant glioma (Boulay, et al, 2009; pubmed:19250537).

Animals homozygous for amorphic mutations of Dmel\brat typically die during the larval stage and exhibit abnormal overproliferation in the brain; there is a dramatic increase in neuroblast number. Using a tissue transplant assay for neoplastic capacity, hemizygous larval brain tissue transplanted into the abdomens of wild-type adult female hosts shows unrestrained and invasive growth. Additional phenotypes have been described using somatic clones or less severe mutations. Many physical and genetic interactions have been described for Dmel\brat; see below and in the brat gene report.

See also related human disease model reports for malignant glioma (FBhh0000399, FBhh0000401, FBhh0000403, FBhh0000404, FBhh0000668).

[updated Mar. 2018 by FlyBase; FBrf0222196]

Disease Summary Information
Disease Summary: cancer, neural stem cell, TRIM2,3-related
OMIM report
Human gene(s) implicated
Symptoms and phenotype

Neural stem cells have the ability to self-renew and give rise to neurons and glial cells. In Drosophila, the role and regulation of neural stem cells (neuroblasts) at multiple stages has been studied extensively. The study of neuroblasts in the development of the larval/adult brain has served as a model for the role of adult stem cells in normal neural development and in tumor formation. Asymmetric cell division, a critical part of the process of stem cell renewal vs. differentiation, has been studied in the context of this system.

Genetics
Cellular phenotype and pathology
Molecular information

The proteins encoded by TRIM3 and TRIM2 are members of the tripartite motif (TRIM) family, also called the 'RING-B-box-coiled-coil' (RBCC) subgroup of RING finger proteins. The TRIM motif includes three zinc-binding domains, a RING, a B-box type 1 and a B-box type 2, and a coiled-coil region. The TRIM3 and TRIM2 proteins localize to cytoplasmic filaments. [Gene Cards, TRIM3, TRIM2; 2018.03.22]

The Drosophila ortholog, brat, has been shown to negatively regulate translation. (FlyBase, brat gene report; 2018.03.22]

External links
Disease synonyms
malignant glioma, TRIM2,3-related
cancer, neuroblast-derived, TRIM2,3-related
brain cancer, TRIM2,3-related
Search term: metastatic phenotype(s)
Ortholog Information
Human gene(s) in FlyBase
    Human gene (HGNC)
    D. melanogaster ortholog (based on DIOPT)
    Comments on ortholog(s)

    Many to many: 2 human to 2 Drosophila.

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

    Many to many: 2 human to 2 Drosophila.

    Other mammalian ortholog(s) used
      D. melanogaster Gene Information (1)
      Gene Snapshot
      brain tumor (brat) encodes a tumor suppressor that regulates proliferation in the brain. During neural stem cell division, it segregates into one daughter cell where it inhibits protein translation, preventing self-renewal and inducing differentiation. It also acts during oogenesis where it interacts with the products of nos and pum to suppress hb translation. [Date last reviewed: 2019-03-07]
      Gene Groups / Pathways
        Comments on ortholog(s)

        Low-scoring ortholog of human TRIM3 and TRIM2 (2 Drosophila to 2 human). Dmel\brat shares 23-25% identity and 39-41% 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 (28 groups)
        protein-protein
        Interacting group
        Assay
        References
        x-ray crystallography
        anti bait coimmunoprecipitation, western blot, two hybrid, peptide massfingerprinting, bimolecular fluorescence complementation, fluorescence microscopy, anti tag coimmunoprecipitation, anti tag western blot
        two hybrid, anti tag coimmunoprecipitation, anti tag western blot, bimolecular fluorescence complementation, fluorescence microscopy
        anti bait coimmunoprecipitation, western blot, anti tag coimmunoprecipitation, anti tag western blot
        molecular sieving, molecular weight estimation by staining, two hybrid, isothermal titration calorimetry, predetermined participant, pull down, anti tag coimmunoprecipitation, anti tag western blot
        molecular sieving, molecular weight estimation by staining, pull down, anti tag western blot, western blot, three hybrid, transcriptional complementation assay
        anti tag coimmunoprecipitation, peptide massfingerprinting
        anti tag coimmunoprecipitation, primer specific pcr, pull down, molecular weight estimation by staining
        two hybrid, bimolecular fluorescence complementation, fluorescence microscopy, anti tag coimmunoprecipitation, anti tag western blot
        anti tag coimmunoprecipitation, anti tag western blot
        RNA-protein
        Interacting group
        Assay
        References
        iclip, partial RNA sequence identification
        anti tag coimmunoprecipitation, primer specific pcr
        anti tag coimmunoprecipitation, primer specific pcr
        electrophoretic mobility shift assay, autoradiography, anti tag coimmunoprecipitation, primer specific pcr
        anti bait coimmunoprecipitation, primer specific pcr
        molecular sieving, static light scattering, microscale thermophoresis, predetermined participant, electrophoretic mobility shift assay, autoradiography, nucleic acid uv cross-linking assay, Identification by mass spectrometry, anti tag coimmunoprecipitation, quantitative reverse transcription pcr
        anti tag coimmunoprecipitation, primer specific pcr, electrophoretic mobility shift assay, autoradiography
        electrophoretic mobility shift assay, autoradiography, anti tag coimmunoprecipitation, primer specific pcr
        anti tag coimmunoprecipitation, quantitative reverse transcription pcr
        anti tag coimmunoprecipitation, primer specific pcr
        anti tag coimmunoprecipitation, primer specific pcr
        anti tag coimmunoprecipitation, primer specific pcr
        anti bait coimmunoprecipitation, northern blot
        anti tag coimmunoprecipitation, primer specific pcr
        anti tag coimmunoprecipitation, primer specific pcr, pull down, molecular weight estimation by staining
        anti tag coimmunoprecipitation, primer specific pcr
        electrophoretic mobility shift assay, autoradiography, anti bait coimmunoprecipitation, quantitative reverse transcription pcr
        Alleles Reported to Model Human Disease (Disease Ontology) (0 alleles)
        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
        ethyl methanesulfonate
        amorphic allele - molecular evidence
        formaldehyde
        ethyl methanesulfonate
        amorphic allele - molecular evidence
        ethyl methanesulfonate
        amorphic allele - molecular evidence
        ethyl methanesulfonate
        References (38)