COP9 signalosome subunit 8 is essential for peripheral T cell homeostasis and antigen receptor-induced entry into the cell cycle from quiescence.
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.
Menon
Suchithra
S
Department of Molecular, Cellular and Developmental Biology, Yale University, New Haven, Connecticut 06511, USA.
Chi
Hongbo
H
Zhang
Huiyong
H
Deng
Xing Wang
XW
Flavell
Richard A
RA
Wei
Ning
N
D019264:Adoptive Transfer; D000818:Animals; D000075686:COP9 Signalosome Complex; D002352:Carrier Proteins / Q000276:immunology / Q000378:metabolism*; D002453:Cell Cycle / Q000502:physiology*; D049109:Cell Proliferation; D005434:Flow Cytometry; D015870:Gene Expression / Q000276:immunology; D005786:Gene Expression Regulation; D006706:Homeostasis / Q000276:immunology*; D015151:Immunoblotting; D007376:Interleukin-2 / Q000096:biosynthesis; D008213:Lymphocyte Activation / Q000276:immunology*; D051379:Mice; D011948:Receptors, Antigen, T-Cell / Q000276:immunology / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology / Q000378:metabolism*
D002352:Carrier Proteins; C481538:Cops8 protein, mouse; D007376:Interleukin-2; D011948:Receptors, Antigen, T-Cell; D000075686:COP9 Signalosome Complex