Your browser doesn't support javascript.
loading
Mammalian ataxin-2 modulates translation control at the pre-initiation complex via PI3K/mTOR and is induced by starvation.
Lastres-Becker, Isabel; Nonis, David; Eich, Florian; Klinkenberg, Michael; Gorospe, Myriam; Kötter, Peter; Klein, Fabrice A C; Kedersha, Nancy; Auburger, Georg.
Afiliação
  • Lastres-Becker I; Section of Molecular Neurogenetics, Dept. of Neurology, Building 89, 3rd floor, Goethe University Medical School, Theodor Stern Kai 7, 60590 Frankfurt am Main, Germany. Electronic address: ilbecker@iib.uam.es.
  • Nonis D; Section of Molecular Neurogenetics, Dept. of Neurology, Building 89, 3rd floor, Goethe University Medical School, Theodor Stern Kai 7, 60590 Frankfurt am Main, Germany.
  • Eich F; Section of Molecular Neurogenetics, Dept. of Neurology, Building 89, 3rd floor, Goethe University Medical School, Theodor Stern Kai 7, 60590 Frankfurt am Main, Germany.
  • Klinkenberg M; Section of Molecular Neurogenetics, Dept. of Neurology, Building 89, 3rd floor, Goethe University Medical School, Theodor Stern Kai 7, 60590 Frankfurt am Main, Germany.
  • Gorospe M; Laboratory of Genetics, National Institute on Aging-Intramural Research Program, National Institutes of Health, Baltimore, MD 21224, USA.
  • Kötter P; Center of Excellence Macromolecular Complexes, Institute of Molecular Biosciences, Goethe-University, 60590 Frankfurt am Main, Germany.
  • Klein FA; Translational Medicine and Neurogenetics Department, Institut de Génétique et Biologie Moléculaire et Cellulaire, UMR7104-CNRS/U964-INSERM/UDS, BP10142, 67404 Illkirch Cédex, France.
  • Kedersha N; Division of Rheumatology, Immunology and Allergy, Brigham and Women's Hospital and Harvard Medical School, One Jimmy Fund Way, Boston, MA 02115, USA.
  • Auburger G; Section of Molecular Neurogenetics, Dept. of Neurology, Building 89, 3rd floor, Goethe University Medical School, Theodor Stern Kai 7, 60590 Frankfurt am Main, Germany. Electronic address: auburger@em.uni-frankfurt.de.
Biochim Biophys Acta ; 1862(9): 1558-69, 2016 09.
Article em En | MEDLINE | ID: mdl-27240544
Ataxin-2 is a cytoplasmic protein, product of the ATXN2 gene, whose deficiency leads to obesity, while its gain-of-function leads to neural atrophy. Ataxin-2 affects RNA homeostasis, but its effects are unclear. Here, immunofluorescence analysis suggested that ataxin-2 associates with 48S pre-initiation components at stress granules in neurons and mouse embryonic fibroblasts, but is not essential for stress granule formation. Coimmunoprecipitation analysis showed associations of ataxin-2 with initiation factors, which were concentrated at monosome fractions of polysome gradients like ataxin-2, unlike its known interactor PABP. Mouse embryonic fibroblasts lacking ataxin-2 showed increased phosphorylation of translation modulators 4E-BP1 and ribosomal protein S6 through the PI3K-mTOR pathways. Indeed, human neuroblastoma cells after trophic deprivation showed a strong induction of ATXN2 transcript via mTOR inhibition. Our results support the notion that ataxin-2 is a nutritional stress-inducible modulator of mRNA translation at the pre-initiation complex.
Assuntos
Palavras-chave

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Fosfatidilinositol 3-Quinases / Serina-Treonina Quinases TOR / Ataxina-2 Limite: Animals / Humans Idioma: En Revista: Biochim Biophys Acta Ano de publicação: 2016 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Fosfatidilinositol 3-Quinases / Serina-Treonina Quinases TOR / Ataxina-2 Limite: Animals / Humans Idioma: En Revista: Biochim Biophys Acta Ano de publicação: 2016 Tipo de documento: Article