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Cutting Edge: Pivotal function of Ubc13 in thymocyte TCR signaling.

The Ubc13 E2 ubiquitin-conjugating enzyme is essential for BCR-, TLR-, and IL-1 receptor (IL-1R)-mediated immune responses. Although Ubc13-deficient mice show defects in BCR-, TLR/IL-1R-, or CD40-mediated activation of mitogen-activated protein kinases, the function of Ubc13 in TCR-mediated signaling and responses remains uncertain. To address this, we here generated T cell-specific conditional Ubc13-deficient mice. The frequency of T lymphocytes was severely reduced in spleens from Ubc13-deficient mice. Moreover, Ubc13-deficient thymocytes displayed defective proliferation in response to anti-CD3/CD28 or PMA/ionophore stimulation. Regarding the signal transduction, although NF-kappaB activation was modestly affected, PMA/ionophore-induced activation of Jnk and p38 was profoundly impaired in Ubc13-deficient thymocytes. In addition, PMA/ionophore-mediated ubiquitination of NF-kappaB essential modulator (NEMO)/IkappaB kinase gamma (IKKgamma) and phosphorylation of TGF-beta-activated kinase 1 (TAK1) were nearly abolished in Ubc13-deficient thymocytes. Thus, Ubc13 plays an important role in thymocyte TCR-mediated signaling and immune responses.

Pubmed ID: 17114420


  • Yamamoto M
  • Sato S
  • Saitoh T
  • Sakurai H
  • Uematsu S
  • Kawai T
  • Ishii KJ
  • Takeuchi O
  • Akira S


Journal of immunology (Baltimore, Md. : 1950)

Publication Data

December 1, 2006

Associated Grants


Mesh Terms

  • Animals
  • Blotting, Western
  • Cell Proliferation
  • Electrophoretic Mobility Shift Assay
  • Enzyme Activation
  • Flow Cytometry
  • Immunoprecipitation
  • Lymphocyte Activation
  • Mice
  • Mice, Transgenic
  • Mitogen-Activated Protein Kinase Kinases
  • NF-kappa B
  • Receptors, Antigen, T-Cell
  • Signal Transduction
  • T-Lymphocytes
  • Ubiquitin-Conjugating Enzymes