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Nat Immunol. 2006 Sep;7(9):962-70. Epub 2006 Jul 23.

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

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  • 1Department of Host Defense, Research Institute for Microbial Diseases, Osaka University, Osaka 565-0871, Japan.


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.

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