Proceedings of the National Academy of Sciences - PNAS, 2009-02, Vol.106 (6), p.1832-1837
2009
Details
- Autor(en) / Beteiligte
- Titel
- Ppp1r15 gene knockout reveals an essential role for translation initiation factor 2 alpha (eIF2α) dephosphorylation in mammalian development
- Ist Teil von
- Proceedings of the National Academy of Sciences - PNAS, 2009-02, Vol.106 (6), p.1832-1837
- Ort / Verlag
- United States: National Academy of Sciences
- Erscheinungsjahr
- 2009
- Link zum Volltext
- Quelle
- Free E-Journal (出版社公開部分のみ）
- Beschreibungen/Notizen
- Diverse cellular stress responses are linked to phosphorylation of serine 51 on the alpha subunit of translation initiation factor 2. The resultant attenuation of protein synthesis and activation of gene expression figure heavily in the adaptive response to stress, but dephosphorylation of eIF2(αP), which terminates signaling in this pathway, is less well understood. GADD34 and CReP, the products of the related mammalian genes Ppp1r15a and Ppp1r15b, can recruit phosphatase catalytic subunits of the PPP1 class to eIF2(αP), but the significance of their contribution to its dephosphorylation has not been explored systematically. Here we report that unlike Ppp1r15a mutant mice, which are superficially indistinguishable from wild type, Ppp1r15b⁻/⁻ mouse embryos survive gestation but exhibit severe growth retardation and impaired erythropoiesis, and loss of both Ppp1r15 genes leads to early embryonic lethality. These loss-of-function phenotypes are rescued by a mutation, Eif2aS⁵¹A, that prevents regulated phosphorylation of eIF2α. These findings reveal that the essential process of eIF2(αP) dephosphorylation is the predominant role of PPP1R15 proteins in mammalian development.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 0027-8424eISSN: 1091-6490DOI: 10.1073/pnas.0809632106Titel-ID: cdi_proquest_miscellaneous_66909905
- Format
- –
- Schlagworte
- Alleles, Animals, Antigens, Differentiation - genetics, Biological Sciences, Cell Cycle Proteins - genetics, dephosphorylation, Embryo, Mammalian, Embryos, Erythropoiesis, Eukaryotic Initiation Factor-2 - metabolism, Eukaryotic Initiation Factor-2 - physiology, Female, Fetal Death, gene activation, Gene expression, Gene expression regulation, Gene Knockout Techniques, gene targeting, genes, Genetic mutation, Genotype & phenotype, Genotypes, Growth and Development - genetics, Growth Disorders, growth retardation, loss-of-function mutation, Mice, mutants, Mutation, Peptide initiation factors, phenotype, Phenotypes, Phosphorylation, pregnancy, Protein Phosphatase 1 - genetics, protein subunits, Protein synthesis, Proteins, Rodents, serine, signal transduction, stress response, translation (genetics)