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General Information
Name
acute myeloid leukemia models, RAS-Scrib-complex-related
FlyBase ID
FBhh0001042
Disease Ontology Term
Parent Disease
OMIM
Overview

In flies, hemocyte-specific expression of an activated form of RAS (Dmel\Ras85DV12) in combination with knockdown of either scrib or l(2)gl results in dramatic increases in hemocyte number (in the range of 100-fold). The animals typically die during the larval or pupal stage. Phenotypes reminiscent of cachexia are observed. Responses to infectious agents have been assessed.

The constitutively active Ras85D mutation, Ras85DV12, is analogous to oncogenic mutations found in human RAS proteins. Variant(s) implicated in human disease tested (as analogous mutation in fly gene): G12V in the fly Ras85D gene (corresponds to G12V in the human KRAS and HRAS genes).

The Scribble polarity complex plays a key role in determining cell polarity and cell proliferation in epithelial cells. Classical amorphic and hypomorphic mutations, RNAi-targeting constructs, and alleles caused by insertional mutagenesis have been generated for both scrib and l(2)gl.

Drosophila cancer models using Ras85DV12 and genes encoding components of the Scribble complex have been developed using epithelial systems. See 'cancer, epithelial, RAS-LLGL-related' (FBhh0000588) and 'cancer, epithelial, RAS-SCRIB-related' (FBhh0000585).

[updated May 2019 by FlyBase; FBrf0222196]

Disease Summary Information
Disease Summary: acute myeloid leukemia models, RAS-Scrib-complex-related
OMIM report
Human gene(s) implicated
Symptoms and phenotype
Genetics
Cellular phenotype and pathology
Molecular information
External links
Disease synonyms
Search term: hyperplastic phenotype(s)
Ortholog Information
Human gene(s) in FlyBase
    Other mammalian ortholog(s) used
      D. melanogaster Gene Information (3)
      Gene Snapshot
      Ras oncogene at 85D (Ras85D) encodes a protein that acts downstream of several cell signals, most notably from Receptor Tyrosine Kinases, to regulate tissue growth and development. When abnormally activated it can direct developmental defects and tissue hyperplasia, mimicking aspects of human disease including Rasopathies and cancer, respectively. [Date last reviewed: 2019-03-14]
      Cellular component (GO)
      Gene Groups / Pathways
      Comments on ortholog(s)

      High-scoring ortholog of human genes KRAS, HRAS, and NRAS (many to many; multiple paralogs and orthologs in both species). Dmel\Ras85D shares 78-86% identity and 86-92% similarity with KRAS, HRAS, and NRAS; for these three human genes, Ras85D is the highest-scoring ortholog in Drosophila.

      Orthologs and Alignments from DRSC
      DIOPT - DRSC Integrative Ortholog Prediction Tool - Click the link below to search for orthologs in Humans
      Gene Snapshot
      scribble (scrib) encodes a scaffolding protein that is part of the conserved machinery regulating apicobasal polarity. It acts with the products of dlg1 and l(2)gl to distinguish the basolateral domain of epithelial cells and neuroblasts, via reciprocally antagonistic interactions with the aPKC/par-6 complex that impacts vesicle trafficking. The product of scrib also organizes synaptic architecture and is implicated in learning and memory. [Date last reviewed: 2019-03-14]
      Molecular function (GO)
      Gene Groups / Pathways
      Comments on ortholog(s)

      Ortholog of human SCRIB and LRRC1 (1 Drosophila to 2 human); Dmel\scrib shares 33% identity and 45% similarity with the human SCRIB gene. The human LRRC1 gene encodes a much smaller protein, corresponding to the amino end of SCRIB and Dmel\scrib; it shares 57% identity and 73% similarity with Dmel\scrib within that extent.

      Orthologs and Alignments from DRSC
      DIOPT - DRSC Integrative Ortholog Prediction Tool - Click the link below to search for orthologs in Humans
      Gene Snapshot
      lethal (2) giant larvae (l(2)gl) encodes a tumor suppressor protein that regulates cell polarity and asymmetric cell division. It acts on the basolateral side of epithelial cells, antagonizing the activity of apical complex proteins encoded by baz, par-6 and aPKC. [Date last reviewed: 2019-09-26]
      Gene Groups / Pathways
      Comments on ortholog(s)

      Moderate- to high-scoring ortholog of human LLGL1 and LLGL2 (1 Drosophila to 2 human). Dmel\l(2)gl shares 34-36% identity and 51-54% 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
      Other Genes Used: Viral, Bacterial, Synthetic (0)
        Summary of Physical Interactions (55 groups)
        protein-protein
        Interacting group
        Assay
        References
        anti tag coimmunoprecipitation, peptide massfingerprinting
        anti tag coimmunoprecipitation, peptide massfingerprinting
        anti tag coimmunoprecipitation, peptide massfingerprinting
        anti tag coimmunoprecipitation, peptide massfingerprinting
        anti tag coimmunoprecipitation, autoradiography, two hybrid
        anti tag coimmunoprecipitation, peptide massfingerprinting
        anti tag coimmunoprecipitation, peptide massfingerprinting
        anti tag coimmunoprecipitation, peptide massfingerprinting
        anti tag coimmunoprecipitation, anti tag western blot
        anti tag coimmunoprecipitation, peptide massfingerprinting
        anti tag coimmunoprecipitation, peptide massfingerprinting
        gtpase assay, autoradiography
        anti tag coimmunoprecipitation, peptide massfingerprinting
        pull down, western blot, two hybrid
        anti tag coimmunoprecipitation, peptide massfingerprinting
        anti tag coimmunoprecipitation, anti tag western blot, two hybrid, pull down
        pull down, anti tag western blot
        anti tag coimmunoprecipitation, peptide massfingerprinting
        anti tag coimmunoprecipitation, peptide massfingerprinting
        anti tag coimmunoprecipitation, peptide massfingerprinting
        anti tag coimmunoprecipitation, peptide massfingerprinting
        anti tag coimmunoprecipitation, peptide massfingerprinting
        anti tag coimmunoprecipitation, peptide massfingerprinting
        anti tag coimmunoprecipitation, peptide massfingerprinting
        anti tag coimmunoprecipitation, anti tag western blot
        protein-protein
        Interacting group
        Assay
        References
        anti tag coimmunoprecipitation, anti tag western blot
        proximity ligation assay, fluorescence microscopy
        colocalization, fluorescence microscopy, inferred by author, anti tag coimmunoprecipitation, western blot, anti bait coimmunoprecipitation, proximity ligation assay
        proximity ligation assay, fluorescence microscopy
        x-ray crystallography, isothermal titration calorimetry, predetermined participant, anti bait coimmunoprecipitation, western blot
        anti tag coimmunoprecipitation, anti tag western blot
        pull down, western blot, anti tag coimmunoprecipitation
        anti tag coimmunoprecipitation, western blot
        anti tag coimmunoprecipitation, western blot
        anti tag coimmunoprecipitation, anti tag western blot
        anti tag coimmunoprecipitation, western blot
        anti tag coimmunoprecipitation, anti tag western blot
        pull down, autoradiography
        anti tag coimmunoprecipitation, western blot
        pull down, autoradiography, two hybrid
        protein-protein
        Interacting group
        Assay
        References
        anti tag coimmunoprecipitation, anti tag western blot
        anti bait coimmunoprecipitation, western blot, anti tag coimmunoprecipitation, peptide massfingerprinting, experimental knowledge based
        anti tag coimmunoprecipitation, western blot
        anti tag coimmunoprecipitation, western blot
        anti tag coimmunoprecipitation, anti tag western blot
        anti tag coimmunoprecipitation, western blot
        anti tag coimmunoprecipitation, western blot
        anti tag coimmunoprecipitation, western blot, anti bait coimmunoprecipitation
        anti tag coimmunoprecipitation, peptide massfingerprinting, pull down, autoradiography, anti bait coimmunoprecipitation, anti tag western blot, western blot, experimental knowledge based
        pull down, Identification by mass spectrometry, proximity ligation assay, fluorescence microscopy, anti tag coimmunoprecipitation, anti tag western blot
        anti tag coimmunoprecipitation, anti tag western blot
        anti tag coimmunoprecipitation, anti tag western blot
        Alleles Reported to Model Human Disease (Disease Ontology) (26 alleles)
        Models Based on Experimental Evidence ( 4 )
        Allele
        Disease
        Evidence
        References
        Modifiers Based on Experimental Evidence ( 11 )
        Allele
        Disease
        Interaction
        References
        model of  cancer
        is ameliorated by Sec6GD11616
        is ameliorated by Sec8KK101531
        is ameliorated by Sec15GD12109
        is ameliorated by Sec151
        is ameliorated by Src64BGD12263
        is exacerbated by Nek2UAS.GFP
        is ameliorated by JraNIG.2275R
        is ameliorated by bskDN.UAS
        is ameliorated by bskHMS00777
        is exacerbated by hepAct.UAS
        is exacerbated by imdUAS.cGa
        is ameliorated by TimpUAS.cPa
        ameliorates  cancer
        model of  prostate cancer
        model of  kidney cancer
        is ameliorated by Pka-C1B3
        is ameliorated by TorΔP
        Models Based on Experimental Evidence ( 6 )
        Modifiers Based on Experimental Evidence ( 6 )
        Allele
        Disease
        Interaction
        References
        model of  carcinoma
        is ameliorated by licGD7546
        is ameliorated by licJF01433
        Models Based on Experimental Evidence ( 5 )
        Modifiers Based on Experimental Evidence ( 3 )
        Allele
        Disease
        Interaction
        References
        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
        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
        loss of function allele
        natural population
        amorphic allele - genetic evidence
        spontaneous
        spontaneous
        amorphic allele - molecular evidence
        ends-out gene targeting
        loss of function allele
        loss of function allele
        P-element activity
        amorphic allele - genetic evidence
        loss of function allele
        ethyl methanesulfonate
        loss of function allele
        ethyl methanesulfonate
        loss of function allele
        ethyl methanesulfonate
        References (4)