RRC ID 67689
Author Hosokawa H, Tanaka T, Kato M, Shinoda K, Tohyama H, Hanazawa A, Tamaki Y, Hirahara K, Yagi R, Sakikawa I, Morita A, Nagira M, Poyurovsky MV, Suzuki Y, Motohashi S, Nakayama T.
Title Gata3/Ruvbl2 complex regulates T helper 2 cell proliferation via repression of Cdkn2c expression.
Journal Proc Natl Acad Sci U S A
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.
Volume 110(46)
Pages 18626-31
Published 2013-11-12
DOI 10.1073/pnas.1311100110
PII 1311100110
PMID 24167278
PMC PMC3832009
MeSH ATPases Associated with Diverse Cellular Activities Animals Bromodeoxyuridine Cell Proliferation* Chromatin Immunoprecipitation Cyclin-Dependent Kinase Inhibitor p18 / metabolism* DNA Helicases / immunology* DNA Primers / genetics GATA3 Transcription Factor / immunology* Gene Expression Regulation / immunology* Gene Knockdown Techniques Immunoblotting Immunoprecipitation Luciferases Mass Spectrometry Mice Mice, Inbred BALB C Mice, Inbred C57BL Multiprotein Complexes / immunology* Real-Time Polymerase Chain Reaction Th2 Cells / cytology*
IF 9.412
DNA material CS-CDF-EG-PRE (RDB04380)