T cell activation signals upregulate CBP-dependent transcriptional activity

Biochem Biophys Res Commun. 2001 Mar 9;281(4):842-50. doi: 10.1006/bbrc.2001.4461.

Abstract

The transcriptional coactivator CREB-binding protein (CBP) is known to play an important role in coupling signal transduction pathways to changes in gene expression. In many cases, this is achieved by the stimulus-specific recruitment of CBP to promoter-bound transcription factors. However, a number of recent studies have suggested that signal transduction pathways can also directly influence CBP-mediated transcriptional activity. Here we show that in Jurkat cells the activity of the CBP C-terminal transactivation domain is strongly upregulated in response to either T cell receptor stimulation or the combination of ionomycin and phorbol ester. We further show that maximal stimulation of CBP-mediated transcription requires the synergistic activation of both the calcineurin and Ras-MAPK signaling pathways. These results indicate that CBP can function as a T cell activation-inducible transcriptional coactivator and is therefore likely to play an important role in T cell activation-induced gene expression.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Antibodies, Monoclonal / pharmacology
  • CD3 Complex / immunology
  • CREB-Binding Protein
  • Calcineurin / metabolism
  • Calcineurin Inhibitors
  • Calcium-Calmodulin-Dependent Protein Kinases / antagonists & inhibitors
  • Calcium-Calmodulin-Dependent Protein Kinases / metabolism
  • DNA, Recombinant
  • Enzyme Inhibitors / pharmacology
  • Flavonoids / pharmacology
  • Gene Expression Regulation / drug effects
  • Humans
  • Ionomycin / pharmacology
  • Ionophores / pharmacology
  • Jurkat Cells
  • Luciferases / genetics
  • Luciferases / metabolism
  • Nuclear Proteins / genetics
  • Nuclear Proteins / physiology*
  • Plasmids / genetics
  • Recombinant Fusion Proteins / genetics
  • Recombinant Fusion Proteins / metabolism
  • Signal Transduction / drug effects
  • T-Lymphocytes / cytology
  • T-Lymphocytes / metabolism*
  • Tacrolimus / pharmacology
  • Tetradecanoylphorbol Acetate / pharmacology
  • Trans-Activators / genetics
  • Trans-Activators / physiology*
  • Transcription, Genetic
  • Transfection
  • Up-Regulation

Substances

  • Antibodies, Monoclonal
  • CD3 Complex
  • Calcineurin Inhibitors
  • DNA, Recombinant
  • Enzyme Inhibitors
  • Flavonoids
  • Ionophores
  • Nuclear Proteins
  • Recombinant Fusion Proteins
  • Trans-Activators
  • Ionomycin
  • Luciferases
  • CREB-Binding Protein
  • CREBBP protein, human
  • Calcium-Calmodulin-Dependent Protein Kinases
  • Calcineurin
  • Tetradecanoylphorbol Acetate
  • 2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one
  • Tacrolimus