Seigo Terawaki    Department   Kawasaki Medical School  Kawasaki Medical School, Department of Molecular and Genetic Medicine,    Position   Assistant Professor with Special Assignment
Article types	原著
Language	English
Peer review	Peer reviewed
Title	Protein phosphatase 1 subunit Ppp1r15a/GADD34 regulates cytokine production in polyinosinic:polycytidylic acid-stimulated dendritic cells.
Journal	Formal name：Proceedings of the National Academy of Sciences of the United States of America Abbreviation：Proc Natl Acad Sci U S A ISSN code：10916490/00278424
Domestic / Foregin	Foregin
Volume, Issue, Page	109(8),pp.3006-3011
Author and coauthor	Clavarino Giovanna, Cláudio Nuno, Dalet Alexandre, Terawaki Seigo, Couderc Thérèse, Chasson Lionel, Ceppi Maurizio, Schmidt Enrico K, Wenger Till, Lecuit Marc, Gatti Evelina, Pierre Philippe
Publication date	2012/02
Summary	In response to inflammatory stimulation, dendritic cells (DCs) have a remarkable pattern of differentiation that exhibits specific mechanisms to control the immune response. Here we show that in response to polyriboinosinic:polyribocytidylic acid (pI:C), DCs mount a specific integrated stress response during which the transcription factor ATF4 and the growth arrest and DNA damage-inducible protein 34 (GADD34/Ppp1r15a), a phosphatase 1 (PP1) cofactor, are expressed. In agreement with increased GADD34 levels, an extensive dephosphorylation of the translation initiation factor eIF2α was observed during DC activation. Unexpectedly, although DCs display an unusual resistance to protein synthesis inhibition induced in response to cytosolic dsRNA, GADD34 expression did not have a major impact on protein synthesis. GADD34, however, was shown to be required for normal cytokine production both in vitro and in vivo. These observations have important implications in linking further pathogen detection with the integrated stress response pathways.
DOI	10.1073/pnas.1104491109
PMID	22315398