mTOR signaling and transcriptional regulation in T lymphocytes

Transcription. 2014;5(2):e28263. doi: 10.4161/trns.28263.

Abstract

The mechanistic target of rapamycin (mTOR) signaling integrates diverse environmental cues, including growth factors, nutrients and immunological signals. Activation of mTOR signaling stimulates protein synthesis and anabolic metabolism and coordinates cell growth, proliferation and fate decisions. In recent years, mTOR signaling has been linked to the entire spectrum of T cell biology, ranging from T cell development and activation to lineage specification and memory formation. Mechanistically, mTOR activation profoundly affects the expression and activity of many immunologically relevant transcription factors to propagate immune signaling and mediate effector functions. These transcription factors orchestrate cell metabolism (MYC, SREBPs and HIF1), lineage differentiation (T-bet, GATA3, RORγt, FOXP3 and Eomesodermin) and immune activation and functions (NF-κB, FOXOs, IRF4, STATs and GFI-1). This review discusses how mTOR signaling, through impinging upon transcriptional factors, regulates T cell development, activation, and effector and memory differentiation.

Keywords: Eukaryotic transcription; transcription factors and co-activators.

MeSH terms

  • Animals
  • Cell Differentiation
  • Gene Expression Regulation*
  • Humans
  • Mechanistic Target of Rapamycin Complex 1
  • Mechanistic Target of Rapamycin Complex 2
  • Multiprotein Complexes / metabolism
  • Signal Transduction*
  • T-Lymphocytes / cytology
  • T-Lymphocytes / metabolism*
  • TOR Serine-Threonine Kinases / metabolism
  • Thymocytes / physiology
  • Transcription Factors / metabolism

Substances

  • Multiprotein Complexes
  • Transcription Factors
  • Mechanistic Target of Rapamycin Complex 1
  • Mechanistic Target of Rapamycin Complex 2
  • TOR Serine-Threonine Kinases