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.
Yamamoto
Masahiro
M
Department of Host Defense, Research Institute for Microbial Diseases, Osaka University, Osaka 565-0871, Japan.
Okamoto
Toru
T
Takeda
Kiyoshi
K
Sato
Shintaro
S
Sanjo
Hideki
H
Uematsu
Satoshi
S
Saitoh
Tatsuya
T
Yamamoto
Naoki
N
Sakurai
Hiroaki
H
Ishii
Ken J
KJ
Yamaoka
Shoji
S
Kawai
Taro
T
Matsuura
Yoshiharu
Y
Takeuchi
Osamu
O
Akira
Shizuo
S
D000818:Animals; D001402:B-Lymphocytes / Q000201:enzymology* / Q000276:immunology; D008213:Lymphocyte Activation / Q000235:genetics; D020930:MAP Kinase Kinase Kinases / Q000378:metabolism; D008262:Macrophage Activation / Q000235:genetics*; D008264:Macrophages / Q000201:enzymology* / Q000276:immunology; D051379:Mice; D008817:Mice, Mutant Strains; D009154:Mutation; D016328:NF-kappa B / Q000819:agonists; D011971:Receptors, Immunologic / Q000378:metabolism*; D015398:Signal Transduction; D044763:Ubiquitin-Conjugating Enzymes / Q000235:genetics / Q000502:physiology*
D016328:NF-kappa B; D011971:Receptors, Immunologic; C514982:Ube2n protein, mouse; D044763:Ubiquitin-Conjugating Enzymes; D020930:MAP Kinase Kinase Kinases