title: Gata3/Ruvbl2 complex regulates T helper 2 cell proliferation via repression of Cdkn2c expression.
abstract: 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 cell 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.
authors.affiliation: Department of Immunology, Department of Clinical Cell Biology, and Division of Endocrinology and Metabolism, Department of Advanced Allegology of the Airway, and Department of Medical Immunology, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba 260-8670, Japan.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Hosokawa
authors.forename: Tomoaki
authors.initials: T
authors.lastname: Tanaka
authors.forename: Miki
authors.initials: M
authors.lastname: Kato
authors.forename: Kenta
authors.initials: K
authors.lastname: Shinoda
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Tohyama
authors.forename: Asami
authors.initials: A
authors.lastname: Hanazawa
authors.forename: Yuuki
authors.initials: Y
authors.lastname: Tamaki
authors.forename: Kiyoshi
authors.initials: K
authors.lastname: Hirahara
authors.forename: Ryoji
authors.initials: R
authors.lastname: Yagi
authors.forename: Ikue
authors.initials: I
authors.lastname: Sakikawa
authors.forename: Atsushi
authors.initials: A
authors.lastname: Morita
authors.forename: Morio
authors.initials: M
authors.lastname: Nagira
authors.forename: Masha V
authors.initials: MV
authors.lastname: Poyurovsky
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Suzuki
authors.forename: Shinichiro
authors.initials: S
authors.lastname: Motohashi
authors.forename: Toshinori
authors.initials: T
authors.lastname: Nakayama
mesh_terms: D000074183:ATPases Associated with Diverse Cellular Activities; D000818:Animals; D001973:Bromodeoxyuridine; D049109:Cell Proliferation; D047369:Chromatin Immunoprecipitation; D050763:Cyclin-Dependent Kinase Inhibitor p18 / Q000378:metabolism*; D004265:DNA Helicases / Q000276:immunology*; D017931:DNA Primers / Q000235:genetics; D050990:GATA3 Transcription Factor / Q000276:immunology*; D005786:Gene Expression Regulation / Q000276:immunology*; D055785:Gene Knockdown Techniques; D015151:Immunoblotting; D047468:Immunoprecipitation; D008156:Luciferases; D013058:Mass Spectrometry; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D046912:Multiprotein Complexes / Q000276:immunology*; D060888:Real-Time Polymerase Chain Reaction; D018418:Th2 Cells / Q000166:cytology*
chemical_list: C493972:Cdkn2c protein, mouse; D050763:Cyclin-Dependent Kinase Inhibitor p18; D017931:DNA Primers; D050990:GATA3 Transcription Factor; C494748:Gata3 protein, mouse; D046912:Multiprotein Complexes; D008156:Luciferases; D000074183:ATPases Associated with Diverse Cellular Activities; D004265:DNA Helicases; C518330:RUVBL2 protein, mouse; D001973:Bromodeoxyuridine
keywords: master transcription factor; polycomb group complex; transcriptional regulation