Article abstract
Nature Immunology 8, 64 - 73 (2006)
Published online: 26 November 2006 | doi:10.1038/ni1413
The kinases aurora B and mTOR regulate the G1–S cell cycle progression of T lymphocytes
Jianxun Song1,2, Shahram Salek-Ardakani1, Takanori So1 & Michael Croft1
Abstract
CD28-deficient T cells arrest at the G1–S transition of the cell cycle. Here we show that this is controlled by the kinase aurora B, which exists in a complex with survivin and mammalian target of rapamycin (mTOR). Expression of aurora B in Cd28-/- T cells augmented phosphorylation of mTOR substrates, expression of cyclin A, hyperphosphorylation of retinoblastoma protein and activation of cyclin-dependent kinases 1 and 2 and promoted cell cycle progression. Interleukin 2 enhanced aurora B activity, and inactive aurora B prevented interleukin 2–induced proliferation. Moreover, expression of aurora B restored Cd28-/- T cell proliferation and promoted inflammation in vivo. These data identify aurora B, along with survivin and mTOR, as a regulator of the G1–S checkpoint in T cells.
- Division of Molecular Immunology, La Jolla Institute for Allergy and Immunology, La Jolla, California 92037, USA.
- Institute of Immunology PLA, The Third Military Medical University, Chongqing, China.
Correspondence to: Michael Croft1 e-mail: mick@liai.org
