Jun turnover is controlled through JNK-dependent phosphorylation of the E3 ligase Itch

Science. 2004 Oct 8;306(5694):271-5. doi: 10.1126/science.1099414. Epub 2004 Sep 9.

Abstract

The turnover of Jun proteins, like that of other transcription factors, is regulated through ubiquitin-dependent proteolysis. Usually, such processes are regulated by extracellular stimuli through phosphorylation of the target protein, which allows recognition by F box-containing E3 ubiquitin ligases. In the case of c-Jun and JunB, we found that extracellular stimuli also modulate protein turnover by regulating the activity of an E3 ligase by means of its phosphorylation. Activation of the Jun amino-terminal kinase (JNK) mitogen-activated protein kinase cascade after T cell stimulation accelerated degradation of c-Jun and JunB through phosphorylation-dependent activation of the E3 ligase Itch. This pathway modulates cytokine production by effector T cells.

Publication types

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

MeSH terms

  • Animals
  • CD28 Antigens / immunology
  • CD4-Positive T-Lymphocytes / immunology
  • CD4-Positive T-Lymphocytes / metabolism*
  • Interferon-gamma / metabolism
  • Interleukins / metabolism
  • Lymphocyte Activation
  • MAP Kinase Kinase Kinase 1*
  • MAP Kinase Kinase Kinases / genetics
  • MAP Kinase Kinase Kinases / metabolism
  • Mice
  • Mitogen-Activated Protein Kinase 8
  • Mitogen-Activated Protein Kinase 9
  • Mitogen-Activated Protein Kinases / metabolism*
  • Phosphorylation
  • Proto-Oncogene Proteins c-jun / genetics
  • Proto-Oncogene Proteins c-jun / metabolism*
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Receptors, Antigen, T-Cell / immunology
  • Recombinant Fusion Proteins / metabolism
  • T-Lymphocytes / immunology
  • T-Lymphocytes / metabolism*
  • Th2 Cells / cytology
  • Th2 Cells / immunology
  • Th2 Cells / metabolism
  • Ubiquitin / metabolism
  • Ubiquitin-Protein Ligases / metabolism*

Substances

  • CD28 Antigens
  • Interleukins
  • Proto-Oncogene Proteins c-jun
  • RNA, Messenger
  • Receptors, Antigen, T-Cell
  • Recombinant Fusion Proteins
  • Ubiquitin
  • Interferon-gamma
  • Itch protein, mouse
  • Ubiquitin-Protein Ligases
  • Mitogen-Activated Protein Kinase 9
  • Mitogen-Activated Protein Kinase 8
  • Mitogen-Activated Protein Kinases
  • MAP Kinase Kinase Kinase 1
  • MAP Kinase Kinase Kinases
  • Map3k1 protein, mouse