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Key function for the Ubc13 E2 ubiquitin-conjugating enzyme in immune receptor signaling.

The Ubc13 E2 ubiquitin-conjugating enzyme is key in the process of 'tagging' target proteins with lysine 63-linked polyubiquitin chains, which are essential for the transmission of immune receptor signals culminating in activation of the transcription factor NF-kappaB. Here we demonstrate that conditional ablation of Ubc13 resulted in defective B cell development and in impaired B cell and macrophage activation. In response to all tested stimuli except tumor necrosis factor, Ubc13-deficient cells showed almost normal NF-kappaB activation but considerably impaired activation of mitogen-activated protein kinase. Ubc13-induced activation of mitogen-activated protein kinase required, at least in part, ubiquitination of the adaptor protein IKKgamma. These results show that Ubc13 is key in the mammalian immune response.

Pubmed ID: 16862162


  • Yamamoto M
  • Okamoto T
  • Takeda K
  • Sato S
  • Sanjo H
  • Uematsu S
  • Saitoh T
  • Yamamoto N
  • Sakurai H
  • Ishii KJ
  • Yamaoka S
  • Kawai T
  • Matsuura Y
  • Takeuchi O
  • Akira S


Nature immunology

Publication Data

September 22, 2006

Associated Grants


Mesh Terms

  • Animals
  • B-Lymphocytes
  • Lymphocyte Activation
  • MAP Kinase Kinase Kinases
  • Macrophage Activation
  • Macrophages
  • Mice
  • Mice, Mutant Strains
  • Mutation
  • NF-kappa B
  • Receptors, Immunologic
  • Signal Transduction
  • Ubiquitin-Conjugating Enzymes