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Gata3/Ruvbl2 complex regulates T helper 2 cell proliferation via repression of Cdkn2c expression.

GATA-binding protein 3 (Gata3) controls the differentiation of naive CD4 T cells into T helper 2 (Th2) cells by induction of chromatin remodeling of the Th2 cytokine gene loci, direct transactivation of Il5 and Il13 genes, and inhibition of Ifng. Gata3 also facilitates Th2 ceil proliferation via add... Full description

Journal Title: Proceedings of the National Academy of Sciences of the United States of America November 12, 2013, Vol.110(46), pp.18626-18631
Main Author: Hosokawa, Hiroyuki
Other Authors: Tanaka, Tomoaki , Kato, Miki , Shinoda, Kenta , Tohyama, Hiroyuki , Hanazawa, Asami , Tamaki, Yuuki , Hirahara, Kiyoshi , Yagi, Ryoji , Sakikawa, Ikue , Morita, Atsushi , Nagira, Morio , Poyurovsky, Masha V , Suzuki, Yutaka , Motohashi, Shinichiro , Nakayama, Toshinori
Format: Electronic Article Electronic Article
Language: English
Subjects:
ID: E-ISSN: 1091-6490 ; DOI: 10.1073/pnas.1311100110
Link: http://search.proquest.com/docview/1458502962/?pq-origsite=primo
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title: Gata3/Ruvbl2 complex regulates T helper 2 cell proliferation via repression of Cdkn2c expression.
format: Article
creator:
  • Hosokawa, Hiroyuki
  • Tanaka, Tomoaki
  • Kato, Miki
  • Shinoda, Kenta
  • Tohyama, Hiroyuki
  • Hanazawa, Asami
  • Tamaki, Yuuki
  • Hirahara, Kiyoshi
  • Yagi, Ryoji
  • Sakikawa, Ikue
  • Morita, Atsushi
  • Nagira, Morio
  • Poyurovsky, Masha V
  • Suzuki, Yutaka
  • Motohashi, Shinichiro
  • Nakayama, Toshinori
subjects:
  • Atpases Associated With Diverse Cellular Activities–Metabolism
  • Animals–Immunology
  • Bromodeoxyuridine–Genetics
  • Cell Proliferation–Immunology
  • Chromatin Immunoprecipitation–Immunology
  • Cyclin-Dependent Kinase Inhibitor P18–Immunology
  • DNA Helicases–Cytology
  • DNA Primers–Cytology
  • Gata3 Transcription Factor–Cytology
  • Gene Expression Regulation–Cytology
  • Gene Knockdown Techniques–Cytology
  • Immunoblotting–Cytology
  • Immunoprecipitation–Cytology
  • Luciferases–Cytology
  • Mass Spectrometry–Cytology
  • Mice–Cytology
  • Mice, Inbred Balb C–Cytology
  • Mice, Inbred C57bl–Cytology
  • Multiprotein Complexes–Cytology
  • Real-Time Polymerase Chain Reaction
ispartof: Proceedings of the National Academy of Sciences of the United States of America, November 12, 2013, Vol.110(46), pp.18626-18631
description: GATA-binding protein 3 (Gata3) controls the differentiation of naive CD4 T cells into T helper 2 (Th2) cells by induction of chromatin remodeling of the Th2 cytokine gene loci, direct transactivation of Il5 and Il13 genes, and inhibition of Ifng. Gata3 also facilitates Th2 ceil proliferation via additional mechanisms that are far less well understood. We herein found that Gata3 associates with RuvB-like protein 2 (Ruvbl2) and represses the expression of a CDK inhibitor, cyclin-dependent kinase inhibitor 2c (Cdkn2c) to facilitate the proliferation of Th2 cells. Gata3 directly bound to the Cdkn2c locus in an Ruvbl2-dependent manner. The defect in the proliferation of Gata3-deficient Th2 cells is rescued by the knockdown of Cdkn2c, indicating that Cdkn2c is a key molecule involved in the Gata3-mediated induction of Th2 cell proliferation. Ruvbl2-knockdown Th2 cells showed decreased antigen-induced expansion and caused less airway inflammation in vivo. We therefore have identified a functional Gata3/Ruvbl2 complex that regulates the proliferation of differentiating Th2 cells through the repression of a CDK inhibitor, Cdkn2c. master transcription factor | transcriptional regulation | polycomb group complex www.pnas.org/cgi/doi/ 10.1073/pnas.1311100110
language: eng
source:
identifier: E-ISSN: 1091-6490 ; DOI: 10.1073/pnas.1311100110
fulltext: fulltext
issn:
  • 10916490
  • 1091-6490
url: Link


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titleGata3/Ruvbl2 complex regulates T helper 2 cell proliferation via repression of Cdkn2c expression.
creatorHosokawa, Hiroyuki ; Tanaka, Tomoaki ; Kato, Miki ; Shinoda, Kenta ; Tohyama, Hiroyuki ; Hanazawa, Asami ; Tamaki, Yuuki ; Hirahara, Kiyoshi ; Yagi, Ryoji ; Sakikawa, Ikue ; Morita, Atsushi ; Nagira, Morio ; Poyurovsky, Masha V ; Suzuki, Yutaka ; Motohashi, Shinichiro ; Nakayama, Toshinori
contributorHosokawa, Hiroyuki (correspondence author) ; Hosokawa, Hiroyuki (record owner)
ispartofProceedings of the National Academy of Sciences of the United States of America, November 12, 2013, Vol.110(46), pp.18626-18631
identifierE-ISSN: 1091-6490 ; DOI: 10.1073/pnas.1311100110
subjectAtpases Associated With Diverse Cellular Activities–Metabolism ; Animals–Immunology ; Bromodeoxyuridine–Genetics ; Cell Proliferation–Immunology ; Chromatin Immunoprecipitation–Immunology ; Cyclin-Dependent Kinase Inhibitor P18–Immunology ; DNA Helicases–Cytology ; DNA Primers–Cytology ; Gata3 Transcription Factor–Cytology ; Gene Expression Regulation–Cytology ; Gene Knockdown Techniques–Cytology ; Immunoblotting–Cytology ; Immunoprecipitation–Cytology ; Luciferases–Cytology ; Mass Spectrometry–Cytology ; Mice–Cytology ; Mice, Inbred Balb C–Cytology ; Mice, Inbred C57bl–Cytology ; Multiprotein Complexes–Cytology ; Real-Time Polymerase Chain Reaction
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descriptionGATA-binding protein 3 (Gata3) controls the differentiation of naive CD4 T cells into T helper 2 (Th2) cells by induction of chromatin remodeling of the Th2 cytokine gene loci, direct transactivation of Il5 and Il13 genes, and inhibition of Ifng. Gata3 also facilitates Th2 ceil proliferation via additional mechanisms that are far less well understood. We herein found that Gata3 associates with RuvB-like protein 2 (Ruvbl2) and represses the expression of a CDK inhibitor, cyclin-dependent kinase inhibitor 2c (Cdkn2c) to facilitate the proliferation of Th2 cells. Gata3 directly bound to the Cdkn2c locus in an Ruvbl2-dependent manner. The defect in the proliferation of Gata3-deficient Th2 cells is rescued by the knockdown of Cdkn2c, indicating that Cdkn2c is a key molecule involved in the Gata3-mediated induction of Th2 cell proliferation. Ruvbl2-knockdown Th2 cells showed decreased antigen-induced expansion and caused less airway inflammation in vivo. We therefore have identified a functional Gata3/Ruvbl2 complex that regulates the proliferation of differentiating Th2 cells through the repression of a CDK inhibitor, Cdkn2c. master transcription factor | transcriptional regulation | polycomb group complex www.pnas.org/cgi/doi/ 10.1073/pnas.1311100110
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titleGata3/Ruvbl2 complex regulates T helper 2 cell proliferation via repression of Cdkn2c expression.
authorHosokawa, Hiroyuki ; Tanaka, Tomoaki ; Kato, Miki ; Shinoda, Kenta ; Tohyama, Hiroyuki ; Hanazawa, Asami ; Tamaki, Yuuki ; Hirahara, Kiyoshi ; Yagi, Ryoji ; Sakikawa, Ikue ; Morita, Atsushi ; Nagira, Morio ; Poyurovsky, Masha V ; Suzuki, Yutaka ; Motohashi,...
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