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CUTTING EDGE |
* Department of Host Defense, Research Institute for Microbial Diseases, Osaka University, Yamada-oka, Suita, Osaka;
Exploratory Research for Advanced Technology, Japan Science and Technology Corporation, Yamada-oka, Suita, Osaka;
Division of Pathogenic Biochemistry, Institute of Natural Medicine, 21st Century Center of Excellence (COE) Program, Toyama Medical and Pharmaceutical University, Toyama, Japan
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-
B 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-B essential modulator (NEMO)/IB kinase 
(IKK) and phosphorylation of TGF-
-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 costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
1 This work was supported by grants from Special Coordination Funds, the Ministry of Education, Culture, Sports, Science and Technology, Research Fellowships of the Japan Society for the Promotion of Science for Young Scientists, The Uehara Memorial Foundation, The Naito Foundation, and Exploratory Research for Advanced Technology, Japan Science and Technology Agency.
2 Address correspondence and reprint requests to Dr. Shizuo Akira, Department of Host Defense, Research Institute for Microbial Diseases, Osaka University, 3-1 Yamada-oka, Suita Osaka 565-0851, Japan. E-mail address: sakira{at}biken.osaka-u.ac.jp
3 Abbreviations used in this paper: MAP, mitogen-activated protein; TAK1, TGF--activated kinase 1; TRAF6, TNFR-associated factor 6; IKK, IB kinase; NEMO, NF-B essential modulator; SP, single positive.
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