PI3 kinase signalling blocks Foxp3 expression by sequestering Foxo factors.
Expression of the regulatory T (T reg) cell-associated transcription factor Foxp3 can be induced by signals from the T cell receptor (TCR), interleukin-2 (IL-2), and transforming growth factor (TGF)-beta. These signals are integrated by a network involving phosphatidylinositol 3 kinase (PI3K), protein kinase B (PKB; here referred to as Akt), and the mammalian target of rapamycin (mTOR). New studies show that the Foxo proteins Foxo1 and Foxo3a, which are inactivated by Akt, drive Foxp3 expression. These studies therefore explain the negative regulation of Foxp3 by PI3K signaling, and add Foxo proteins to the growing list of nuclear factors capable of modulating Foxp3 expression.
Merkenschlager
Matthias
M
Lymphocyte Development Group, Medical Research Council Clinical Sciences Centre, Imperial College London, London W12 0NN, UK. matthias.merkenschlager@csc.mrc.ac.uk
von Boehmer
Harald
H
D000818:Animals; D017124:Conserved Sequence; D051858:Forkhead Transcription Factors / Q000378:metabolism*; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism; D008954:Models, Biological; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D015398:Signal Transduction; D058570:TOR Serine-Threonine Kinases
D051858:Forkhead Transcription Factors; D047908:Intracellular Signaling Peptides and Proteins; D019869:Phosphatidylinositol 3-Kinases; D017346:Protein Serine-Threonine Kinases; D051057:Proto-Oncogene Proteins c-akt; D058570:TOR Serine-Threonine Kinases; C546842:MTOR protein, human