The kinases aurora B and mTOR regulate the G1-S cell cycle progression of T lymphocytes.
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.
Song
Jianxun
J
Division of Molecular Immunology, La Jolla Institute for Allergy and Immunology, La Jolla, California 92037, USA.
Salek-Ardakani
Shahram
S
So
Takanori
T
Croft
Michael
M
D000818:Animals; D064107:Aurora Kinase B; D064127:Aurora Kinases; D018106:CD28 Antigens / Q000235:genetics; D002478:Cells, Cultured; D016193:G1 Phase / Q000502:physiology*; D051034:Inhibitor of Apoptosis Proteins; D051379:Mice; D008822:Mice, Transgenic; D008869:Microtubule-Associated Proteins / Q000378:metabolism*; D011494:Protein Kinases / Q000502:physiology*; D017346:Protein Serine-Threonine Kinases / Q000502:physiology*; D015375:Receptors, Interleukin-2 / Q000378:metabolism; D012097:Repressor Proteins; D016196:S Phase / Q000502:physiology*; D015398:Signal Transduction; D000077022:Survivin; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology*; D058570:TOR Serine-Threonine Kinases
C117749:Birc5 protein, mouse; D018106:CD28 Antigens; D051034:Inhibitor of Apoptosis Proteins; D008869:Microtubule-Associated Proteins; D015375:Receptors, Interleukin-2; D012097:Repressor Proteins; D000077022:Survivin; D011494:Protein Kinases; C546843:mTOR protein, mouse; C576924:Aurkb protein, mouse; D064107:Aurora Kinase B; D064127:Aurora Kinases; D017346:Protein Serine-Threonine Kinases; D058570:TOR Serine-Threonine Kinases