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. Author manuscript; available in PMC: 2013 Dec 30.
Published in final edited form as: Nat Rev Immunol. 2012 Sep;12(9):10.1038/nri3278. doi: 10.1038/nri3278

Figure 1. A signalling scheme regulating FOXO transcription factors.

Figure 1

Forkhead box O (FOXO) transcription factors make multiple connections with the cellular signalling network. Examples of connecting proteins include: phosphoinositide 3-kinase (PI3K) and AKT29,30,173–175; ataxia telangiectasia mutated (ATM)176,177; tuberous sclerosis protein 2 (TSC2)178; extracellular signal-regulated kinase (ERK)179; JUN N-terminal kinase (JNK)180; mammalian STE20-like kinase 1 (MST1)49,181; IκB kinase (IKK)42,182; mammalian target of rapamycin (mTOR)25; and CREB-binding protein (CBP)183. The mTOR pathway is inhibited in T cells by metformin, 5-aminoimidazole-4-carboxamide riboside (AICAR)159 and rapamycin160. FOXO transcription factors also affect glycolysis54. γc, γ-chain; 4EBP, EIF4E-binding protein 1; AMPK, AMP-activated protein kinase; BCL-6, B cell lymphoma 6; CTLA4, cytotoxic T lymphocyte antigen 4; EOMES, eomesodermin; IL-7Rα, interleukin-7 receptor subunit-α; KLF2, Krüppel-like factor 2; mTORC, mTOR complex; PDK1, 3-phosphoinositide-dependent kinase 1; ROS, reactive oxygen species; S1P1, sphingosine-1-phosphate receptor 1; S6K1, S6 kinase 1; SIRT1, sirtuin 1; TCR, T cell receptor.