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General Information
Name
cancer, malignant glioma, Par-complex-related
FlyBase ID
FBhh0000936
Disease Ontology Term
Parent Disease
OMIM
Overview

This report describes a model of malignant glioma using the Drosophila Par complex gene aPKC. In Drosophila, the Par complex consists of Dmel\baz (PARD3, PARD3B in human), Dmel\Cdc42 (CDC42 in human), Dmel\par-6 (PARD6A, PARD6B, PARD6G in human) and Dmel\aPKC (PRKCI, PRKCZ in human). This complex is variously called the PAR3-aPKC-PAR6 complex, the Cdc42-Par6-aPKC complex, the aPKC-PAR complex, or other combinations of the components; the junctional apical-basal polarity complex or the junctional ABP complex. The four component fly genes have been extensively studied: classical loss-of-function mutations, RNAi-targeting constructs, and alleles caused by insertional mutagenesis have been generated for each; physical and genetic interactions have been described for each; see below and in the respective gene reports.

Multiple Drosophila genes of the Par complex have been investigated in models of epithelial cancer (see FBhh0000810).

Animals homozygous for severe loss-of-function alleles of Dmel\aPKC typically die in the embryonic or early larval stages; homozygous larvae have a reduced number of brain neuroblasts. When aPKC is overexpressed in the larval and adult brain, hyperplastic proliferation is observed, resulting in masses of undifferentiated immature neural progenitor cells. These undifferentiated masses continue to proliferate, escape proper controls during metamorphosis, and persist in the adult, where they keep growing and result in reduced adult lifespan. Many physical and genetic interactions have been described for Dmel\aPKC; see below and in the aPKC gene report.

[updated Dec. 2018 by FlyBase; FBrf0222196]

Disease Summary Information
Disease Summary: cancer, malignant glioma, Par-complex-related
OMIM report
Human gene(s) implicated
Symptoms and phenotype
Genetics
Cellular phenotype and pathology
Molecular information
PRKCI and PRKCZ encode members of the protein kinase C (PKC) family of serine/threonine protein kinases. The PKC family comprises at least eight members, which are differentially expressed and are involved in a wide variety of cellular processes. Unlike the classical PKC isoenzymes which are calcium-dependent and/or diacylglycerol(DAG)-dependent, PRKCI and PRKCZ protein activities are calcium- and DAG-independent. [Gene Cards, PRKCI, PRKCZ; 2018.12.12]
External links
Disease synonyms
cancer, malignant glioma, PRKC-related
Search term: Par3/Par6/aPKC complex
Search term: aPKC/Par3/Par6 complex
Search term: PAR3-aPKC-PAR6 complex
Search term: aPKC-PAR complex
Search term: Cdc42-Par6-aPKC complex
Search term: junctional apical-basal polarity complex
Search term: junctional ABP complex
Search term: Partitioning-defective complex
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
      atypical protein kinase C (aPKC) encodes a member of the conserved Par complex and is asymmetrically localized to the apical cortex, where it phosphorylates and thus excludes the basal determinants encoded by mira and numb. It is involved in neuroblast proliferation and self-renewal. [Date last reviewed: 2019-03-07]
      Gene Groups / Pathways
      Comments on ortholog(s)
      Moderate- to high-scoring ortholog of human PRKCI and PRKCZ (1 Drosophila to 2 human). Dmel\aPKC shares 60-63% identity and 70-74% 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 (32 groups)
      RNA-protein
      Interacting group
      Assay
      References
      anti bait coimmunoprecipitation, quantitative reverse transcription pcr
      anti bait coimmunoprecipitation, quantitative reverse transcription pcr, pull down, western blot, electrophoretic mobility shift assay, autoradiography
      protein-protein
      Interacting group
      Assay
      References
      enzymatic study, autoradiography
      anti bait coimmunoprecipitation, western blot
      anti bait coimmunoprecipitation, western blot
      pull down, western blot, anti tag western blot, phenotype-based detection assay, fluorescence microscopy, inferred by author
      anti bait coimmunoprecipitation, Identification by mass spectrometry, pull down, autoradiography, western blot
      enzymatic study, Identification by mass spectrometry
      anti tag coimmunoprecipitation, western blot
      anti tag coimmunoprecipitation, western blot
      anti bait coimmunoprecipitation, western blot, anti tag coimmunoprecipitation, peptide massfingerprinting, experimental knowledge based
      anti bait coimmunoprecipitation, western blot, proximity ligation assay, fluorescence microscopy
      anti bait coimmunoprecipitation, western blot, anti tag coimmunoprecipitation, anti tag western blot, enzymatic study, autoradiography, pull down
      anti bait coimmunoprecipitation, western blot, anti tag coimmunoprecipitation, anti tag western blot
      two hybrid, pull down, autoradiography
      anti tag coimmunoprecipitation, western blot, pull down, protein kinase assay, autoradiography, peptide massfingerprinting
      pull down, western blot
      anti tag coimmunoprecipitation, western blot, peptide massfingerprinting
      experimental knowledge based, anti bait coimmunoprecipitation, western blot, anti tag coimmunoprecipitation, peptide massfingerprinting, two hybrid, pull down, autoradiography, anti tag western blot
      pull down, western blot, anti tag western blot
      anti tag coimmunoprecipitation, western blot
      pull down, western blot
      anti tag coimmunoprecipitation, western blot
      anti bait coimmunoprecipitation, anti tag western blot
      anti bait coimmunoprecipitation, western blot
      anti tag coimmunoprecipitation, anti tag western blot, anti bait coimmunoprecipitation
      anti tag coimmunoprecipitation, anti tag western blot
      anti bait coimmunoprecipitation, western blot
      anti tag coimmunoprecipitation, western blot
      anti bait coimmunoprecipitation, western blot
      pull down, western blot, enzymatic study, autoradiography, peptide massfingerprinting, anti bait coimmunoprecipitation
      Alleles Reported to Model Human Disease (Disease Ontology) (2 alleles)
      Models Based on Experimental Evidence ( 1 )
      Allele
      Disease
      Evidence
      References
      Modifiers Based on Experimental Evidence ( 1 )
      Allele
      Disease
      Interaction
      References
      model of  cancer
      is NOT ameliorated by bskK53R.UAS
      Genetic Tools, Stocks and Reagents
      References (6)