The kinases aurora B and mTOR regulate the G1-S cell cycle progression of T lymphocytes

Nat Immunol. 2007 Jan;8(1):64-73. doi: 10.1038/ni1413. Epub 2006 Nov 26.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Aurora Kinase B
  • Aurora Kinases
  • CD28 Antigens / genetics
  • Cells, Cultured
  • G1 Phase / physiology*
  • Inhibitor of Apoptosis Proteins
  • Mice
  • Mice, Transgenic
  • Microtubule-Associated Proteins / metabolism*
  • Protein Kinases / physiology*
  • Protein-Serine-Threonine Kinases / physiology*
  • Receptors, Interleukin-2 / metabolism
  • Repressor Proteins
  • S Phase / physiology*
  • Signal Transduction
  • Survivin
  • T-Lymphocytes / cytology
  • T-Lymphocytes / immunology*
  • TOR Serine-Threonine Kinases

Substances

  • Birc5 protein, mouse
  • CD28 Antigens
  • Inhibitor of Apoptosis Proteins
  • Microtubule-Associated Proteins
  • Receptors, Interleukin-2
  • Repressor Proteins
  • Survivin
  • Protein Kinases
  • TOR Serine-Threonine Kinases
  • mTOR protein, mouse
  • Aurkb protein, mouse
  • Aurora Kinase B
  • Aurora Kinases
  • Protein-Serine-Threonine Kinases