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.
Original language | English |
---|---|
Pages (from-to) | 64-73 |
Number of pages | 10 |
Journal | Nature Immunology |
Volume | 8 |
Issue number | 1 |
DOIs | |
Publication status | Published - 2007 Jan |
ASJC Scopus subject areas
- Immunology and Allergy
- Immunology