Article abstract
Nature Immunology 8, 1236 - 1245 (2007)
Published online: 30 September 2007 | doi:10.1038/ni1514
COP9 signalosome subunit 8 is essential for peripheral T cell homeostasis and antigen receptor–induced entry into the cell cycle from quiescence
Suchithra Menon1,4, Hongbo Chi2,3,4, Huiyong Zhang1, Xing Wang Deng1, Richard A Flavell2 & Ning Wei1
Abstract
Engagement of antigen receptors triggers the proliferation and functional activation of lymphocytes. Here we report that T cell homeostasis and antigen-induced responses require the COP9 signalosome (CSN), a regulator of the ubiquitin-proteasome system. Conditional deletion of the CSN subunit Csn8 in peripheral T lymphocytes disrupted formation of the CSN complex, reduced T cell survival and proliferation in vivo and impaired antigen-induced production of interleukin 2. Moreover, Csn8-deficient T cells showed defective entry into the cell cycle from the G0 quiescent state. This phenotype was associated with a lack of signal-induced expression of cell cycle–related genes, including G1 cyclins and cyclin-dependent kinases, and with excessive induction of p21Cip1. Our data define a CSN-dependent pathway of transcriptional control that is essential for antigen-induced initiation of T cell proliferation.
- Department of Molecular, Cellular and Developmental Biology, Yale University, New Haven, Connecticut 06511, USA.
- Howard Hughes Medical Institute, Department of Immunobiology, Yale University School of Medicine, New Haven, Connecticut 06520, USA.
- Department of Immunology, St. Jude Children's Research Hospital, Memphis, Tennessee 38105, USA.
- These authors contributed equally to this work.
Correspondence to: Ning Wei1 e-mail: ning.wei@yale.edu
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