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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.

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.

Pubmed ID: 17906629

Authors

  • Menon S
  • Chi H
  • Zhang H
  • Deng XW
  • Flavell RA
  • Wei N

Journal

Nature immunology

Publication Data

November 22, 2007

Associated Grants

  • Agency: NIGMS NIH HHS, Id: R01-GM61812
  • Agency: NIGMS NIH HHS, Id: R37-GM047850

Mesh Terms

  • Adoptive Transfer
  • Animals
  • Carrier Proteins
  • Cell Cycle
  • Cell Proliferation
  • Flow Cytometry
  • Gene Expression
  • Gene Expression Regulation
  • Homeostasis
  • Immunoblotting
  • Interleukin-2
  • Lymphocyte Activation
  • Mice
  • Receptors, Antigen, T-Cell
  • Reverse Transcriptase Polymerase Chain Reaction
  • T-Lymphocytes