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General Information
Name
cancer, multiple, TP53-related
FlyBase ID
FBhh0000340
Disease Ontology Term
Parent Disease
OMIM
Overview

The TP53 (p53) gene encodes a tumor suppressor protein containing transcriptional activation, DNA binding, and oligomerization domains. The encoded protein responds to diverse cellular stresses to regulate expression of target genes, thereby inducing cell cycle arrest, apoptosis, senescence, DNA repair, or changes in metabolism. The protective function of TP53 as a tumor suppressor is lost in more than 50% of human cancers. TP53 is implicated in several hereditary cancers, including Li-Fraumeni syndrome (OMIM:191170). There is a single fly ortholog, Dmel\p53, for which classical amorphic and hypomorphic alleles, RNAi-targeting constructs, and alleles caused by insertional mutagenesis have been generated. Dmel\p53 is orthologous to two additional human genes, TP63 and TP73.

Multiple different UAS constructs of the human gene Hsap\TP53 have been introduced into flies; heterologous rescue (functional complementation) using the wild-type human gene has been demonstrated. Constructs of human Hsap\TP53 carrying variants associated with human cancers have been characterized in the fly system. Variant(s) implicated in human disease tested (as transgenic human gene, TP53): the R175H, G245S, R248Q, R273C and R273H variant forms of the human gene have been introduced into flies.

A role for TP53 in regulating transposons and other repetitive elements has been studied in mammalian systems; work using the endogenous fly gene, p53, and introduced copies of the human Hsap\TP53 gene demonstrated that both wild-type genes restrict retrotransposon activity, but mutant forms do not. In this context, the hypothesis that tumor suppression by TP53 may have been co-opted from ancestral functions that acted to contain retrotransposon activity is discussed (FBrf0230578).

Amorphic mutations in the fly p53 gene are viable, but show abnormal stress responses, including to conditions that typically induce apoptosis (reduced levels of apoptosis observed). Multiple genetic and physical interactions of Dmel\p53 have been described; see below and in the gene report for p53.

Dmel\p53 mutant animals have been used to screen drug candidates for enhancement of effects of ionizing radiation in cancer treatment.

Dmel\p53 has been found to play a role in regulated necrosis during spermatogenesis, a non-apoptotic mechanism used to control germ cell number; see the human disease model report 'cancer, multiple, regulators of necrosis' (FBhh0001067). This function is conserved in vertebrate spermatogenesis, thus raising the possibility of targeting an alternative pathway in cancers that are refractory to apoptosis.

[updated Feb. 2020 by FlyBase; FBrf0222196]

Disease Summary Information
Disease Summary: cancer, multiple, TP53-related
OMIM report
Human gene(s) implicated
Symptoms and phenotype
Genetics

The protective function of TP53 as a tumor suppressor is lost in more than 50% of human cancers (Kim and An, 2016: pubmed:27368003).

Cellular phenotype and pathology
Molecular information

The transcription factor TP53 (p53) responds to diverse cellular stresses to regulate target genes that induce cell cycle arrest, apoptosis, senescence, DNA repair, or changes in metabolism. In addition, TP53 appears to induce apoptosis through nontranscriptional cytoplasmic processes. In unstressed cells, TP53 is kept inactive through the actions of the ubiquitin ligase MDM2, which inhibits TP53 transcriptional activity and ubiquitinates TP53 to promote its degradation (Toledo and Wahl, 2006; pubmed:17128209). [from OMIM:191170; 2016.07.06]

The TP53 gene encodes a tumor suppressor protein containing transcriptional activation, DNA binding, and oligomerization domains. The encoded protein responds to diverse cellular stresses to regulate expression of target genes, thereby inducing cell cycle arrest, apoptosis, senescence, DNA repair, or changes in metabolism. [Gene Cards, TP53; 2019.06.27]

External links
Disease synonyms
cancer, multiple, p53-related
Ortholog Information
Human gene(s) in FlyBase
Human gene (HGNC)
D. melanogaster ortholog (based on DIOPT)
Comments on ortholog(s)

Many to one: 3 human to 1 Drosophila; additional orthologous human genes are TP63 and TP73.

Other mammalian ortholog(s) used
    D. melanogaster Gene Information (1)
    Gene Snapshot
    p53 (p53) encodes a transcriptional factor required for adaptive responses to genotoxic stress, including cell death, compensatory proliferation and DNA repair. [Date last reviewed: 2019-03-14]
    Gene Groups / Pathways
    Comments on ortholog(s)

    High-scoring ortholog of human genes TP53, TP63 and TP73 (1 Drosophila to many human). Dmel\p53 shares 20-24% identity and 36-41% 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 (135 groups)
    protein-protein
    Interacting group
    Assay
    References
    coimmunoprecipitation, anti tag western blot, pull down, autoradiography, anti tag coimmunoprecipitation, western blot
    pull down, autoradiography
    bimolecular fluorescence complementation, fluorescence microscopy
    pull down, western blot, anti tag coimmunoprecipitation, anti tag western blot
    pull down, autoradiography
    pull down, autoradiography
    anti tag coimmunoprecipitation, peptide massfingerprinting, experimental knowledge based
    pull down, autoradiography
    pull down, autoradiography
    pull down, autoradiography
    pull down, autoradiography
    pull down, autoradiography
    pull down, autoradiography
    pull down, autoradiography
    pull down, autoradiography
    anti tag coimmunoprecipitation, western blot
    pull down, autoradiography
    pull down, autoradiography
    pull down, autoradiography
    pull down, autoradiography
    pull down, autoradiography
    pull down, autoradiography
    two hybrid array, anti tag coimmunoprecipitation, peptide massfingerprinting, experimental knowledge based
    pull down, autoradiography
    pull down, autoradiography
    pull down, autoradiography
    pull down, autoradiography
    pull down, autoradiography
    pull down, autoradiography
    pull down, autoradiography
    pull down, autoradiography
    pull down, autoradiography
    pull down, autoradiography
    pull down, autoradiography
    pull down, autoradiography
    pull down, autoradiography
    pull down, autoradiography
    pull down, autoradiography
    pull down, autoradiography
    pull down, autoradiography
    pull down, autoradiography
    pull down, autoradiography
    pull down, western blot, anti tag coimmunoprecipitation, anti tag western blot, autoradiography
    pull down, autoradiography
    pull down, autoradiography
    anti tag coimmunoprecipitation, western blot, two hybrid
    pull down, autoradiography
    pull down, autoradiography
    pull down, autoradiography
    pull down, autoradiography, two hybrid
    anti tag coimmunoprecipitation, peptide massfingerprinting, experimental knowledge based
    pull down, autoradiography
    pull down, autoradiography
    pull down, autoradiography
    pull down, autoradiography
    pull down, autoradiography
    pull down, autoradiography
    pull down, autoradiography
    anti bait coimmunoprecipitation, western blot, pull down
    pull down, autoradiography
    pull down, autoradiography
    pull down, autoradiography
    anti bait coimmunoprecipitation, western blot
    pull down, autoradiography
    pull down, autoradiography
    anti tag coimmunoprecipitation, peptide massfingerprinting, experimental knowledge based
    anti bait coimmunoprecipitation, western blot, anti tag coimmunoprecipitation, peptide massfingerprinting, experimental knowledge based
    anti bait coimmunoprecipitation, western blot
    pull down, autoradiography
    pull down, autoradiography
    pull down, autoradiography
    pull down, autoradiography
    pull down, autoradiography
    pull down, autoradiography
    pull down, autoradiography
    two hybrid, pull down, autoradiography
    pull down, autoradiography
    pull down, autoradiography
    anti tag coimmunoprecipitation, western blot, anti bait coimmunoprecipitation, anti tag western blot, pull down, autoradiography
    pull down, autoradiography
    pull down, autoradiography
    pull down, autoradiography
    pull down, autoradiography
    pull down, autoradiography
    pull down, autoradiography
    pull down, autoradiography
    pull down, autoradiography
    pull down, autoradiography
    pull down, autoradiography
    two hybrid array, bimolecular fluorescence complementation, fluorescence microscopy
    pull down, autoradiography
    pull down, autoradiography
    pull down, autoradiography
    pull down, autoradiography
    pull down, autoradiography
    pull down, autoradiography
    pull down, autoradiography
    enzymatic study, western blot
    anti tag coimmunoprecipitation, western blot
    pull down, autoradiography
    pull down, autoradiography
    pull down, autoradiography
    pull down, autoradiography, two hybrid
    pull down, autoradiography
    two hybrid, pull down, autoradiography
    anti tag coimmunoprecipitation, peptide massfingerprinting, experimental knowledge based
    pull down, autoradiography
    anti bait coimmunoprecipitation, western blot
    pull down, autoradiography
    pull down, autoradiography
    pull down, autoradiography
    pull down, autoradiography, two hybrid array
    pull down, autoradiography
    pull down, autoradiography
    two hybrid, pull down, autoradiography
    coimmunoprecipitation, anti tag western blot, pull down, western blot, anti tag coimmunoprecipitation
    bimolecular fluorescence complementation, fluorescence microscopy
    pull down, autoradiography
    enzymatic study, western blot
    anti bait coimmunoprecipitation, western blot
    pull down, autoradiography
    anti tag coimmunoprecipitation, anti tag western blot
    RNA-RNA
    Interacting group
    Assay
    References
    fluorescence technology, luminiscence technology
    luminiscence technology
    luminiscence technology, fluorescence technology
    fluorescence technology, necessary binding region, luminiscence technology
    luminiscence technology
    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
    loss of function allele
    amorphic allele - molecular evidence
    Delta2-3 transposase
    amorphic allele - molecular evidence
    Delta2-3 transposase
    References (31)