title: Drosophila p53-related protein kinase is required for PI3K/TOR pathway-dependent growth.
abstract: Cell growth and proliferation are pivotal for final organ and body size definition. p53-related protein kinase (Bud32/PRPK) has been identified as a protein involved in proliferation through its effects on transcription in yeast and p53 stabilization in human cell culture. However, the physiological function of Bud32/PRPK in metazoans is not well understood. In this work, we have analyzed the role of PRPK in Drosophila development. Drosophila PRPK is expressed in every tissue analyzed and is required to support proliferation and cell growth. The Prpk knockdown animals show phenotypes similar to those found in mutants for positive regulators of the PI3K/TOR pathway. This pathway has been shown to be fundamental for animal growth, transducing the hormonal and nutritional status into the protein translation machinery. Functional interactions have established that Prpk operates as a transducer of the PI3K/TOR pathway, being essential for TOR kinase activation and for the regulation of its targets (S6K and 4E-BP, autophagy and bulk endocytosis). This suggests that Prpk is crucial for stimulating the basal protein biosynthetic machinery in response to insulin signaling and to changes in nutrient availability.
authors: FONDAP Center for Genome Regulation, Departamento de Biología, Facultad de Ciencias, Universidad de Chile, Las Palmeras 3425, Santiago, Chile.
authors: Consuelo
authors: C
authors: Ibar
authors: Vicente F
authors: VF
authors: Cataldo
authors: Constanza
authors: C
authors: Vásquez-Doorman
authors: Patricio
authors: P
authors: Olguín
authors: Alvaro
authors: A
authors: Glavic
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D049109:Cell Proliferation; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D004331:Drosophila melanogaster / Q000196:embryology / Q000235:genetics / Q000254:growth & development* / Q000378:metabolism; D004625:Embryo, Nonmammalian; D005260:Female; D007814:Larva / Q000235:genetics / Q000254:growth & development / Q000378:metabolism; D038081:Organogenesis / Q000235:genetics / Q000502:physiology; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D015398:Signal Transduction / Q000235:genetics / Q000502:physiology; D058570:TOR Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D014921:Wings, Animal / Q000196:embryology / Q000254:growth & development / Q000378:metabolism
chemical_list: D029721:Drosophila Proteins; D019869:Phosphatidylinositol 3-Kinases; D017346:Protein Serine-Threonine Kinases; D058570:TOR Serine-Threonine Kinases; D016159:Tumor Suppressor Protein p53; C474203:p53 protein, Drosophila; C580766:PRPK protein, Drosophila