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 thymo-cytes displayed defective proliferation in response to antiCD3/CD28 or PMA/ionophore stimulation. Regarding the signal transduction, although NF-kappa B activation was modestly affected, PMA/ionophore-induced activation of Jnk and p38 was profoundly impaired in Ubc13-deficient thymocytes.. In addition, PMA/ionopbore-mediated ubiquitination of NF-kappa B essential modulator (NEMO)/I kappa B kinase gamma (IKK gamma) 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, The Journal of Immunology, 2006, 177: 7520-7524.