Direct involvement of the ubiquitin-conjugating enzyme Ubc9/Hus5 in the degradation of IkappaBalpha.
The NF-kappaB/Rel proteins are sequestered in the cytoplasm in association with IkappaBalpha. In response to external signals, IkappaBalpha is phosphorylated, multi-ubiquitinated, and degraded by proteasomes, thereby releasing NF-kappaB/Rel proteins to migrate to the nucleus. We have cloned a mouse ubiquitin-conjugating enzyme (mE2), which associates with IkappaBalpha. mE2 is homologous to the yeast Ubc9/Hus5 ubiquitin-conjugating enzyme. A transdominant-negative mutant of mE2 had no effect on phosphorylation of IkappaBalpha, but delayed its degradation. Correspondingly, tumor necrosis factor-alpha-inducible NF-kappaB activity was diminished. We propose that mE2 is directly involved in the ubiquitin conjugation of IkappaBalpha, a pivotal step in its degradation pathway.
Tashiro
K
K
Laboratory of Genetics, The Salk Institute for Biological Studies, La Jolla, CA 92037, USA.
Pando
M P
MP
Kanegae
Y
Y
Wamsley
P M
PM
Inoue
S
S
Verma
I M
IM
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002460:Cell Line; D003001:Cloning, Molecular; D018076:DNA, Complementary; D004268:DNA-Binding Proteins / Q000378:metabolism*; D005656:Fungal Proteins / Q000235:genetics / Q000378:metabolism*; D005799:Genes, Dominant; D006868:Hydrolysis; D020672:I-kappa B Proteins; D008025:Ligases / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008969:Molecular Sequence Data; D016296:Mutagenesis; D000072000:NF-KappaB Inhibitor alpha; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000378:metabolism; D011485:Protein Binding; D029702:Schizosaccharomyces pombe Proteins; D044763:Ubiquitin-Conjugating Enzymes; D000098843:Ubiquitin-Conjugating Enzyme UBC9
D018076:DNA, Complementary; D004268:DNA-Binding Proteins; D005656:Fungal Proteins; D020672:I-kappa B Proteins; D016328:NF-kappa B; C000606205:Nfkbia protein, mouse; D029702:Schizosaccharomyces pombe Proteins; D000072000:NF-KappaB Inhibitor alpha; D044763:Ubiquitin-Conjugating Enzymes; D008025:Ligases; C093855:HUS5 protein, S pombe; D000098843:Ubiquitin-Conjugating Enzyme UBC9