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1: Nat Immunol. 2007 Nov;8(11):1236-45. Epub 2007 Sep 30.
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COP9 signalosome subunit 8 is essential for peripheral T cell homeostasis and antigen receptor-induced entry into the cell cycle from quiescence.

Menon S, Chi H, Zhang H, Deng XW, Flavell RA, Wei N.

Department of Molecular, Cellular and Developmental Biology, Yale University, New Haven, Connecticut 06511, USA.

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 p21(Cip1). Our data define a CSN-dependent pathway of transcriptional control that is essential for antigen-induced initiation of T cell proliferation.

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PMID: 17906629 [PubMed - indexed for MEDLINE]