Abstract
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.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Amino Acid Sequence
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Animals
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Base Sequence
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Cell Line
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Cloning, Molecular
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DNA, Complementary
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DNA-Binding Proteins / metabolism*
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Fungal Proteins / genetics
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Fungal Proteins / metabolism*
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Genes, Dominant
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Hydrolysis
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I-kappa B Proteins*
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Ligases / genetics
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Ligases / metabolism*
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Mice
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Molecular Sequence Data
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Mutagenesis
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NF-KappaB Inhibitor alpha
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NF-kappa B / antagonists & inhibitors
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NF-kappa B / metabolism
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Protein Binding
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Schizosaccharomyces pombe Proteins*
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Ubiquitin-Conjugating Enzymes*
Substances
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DNA, Complementary
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DNA-Binding Proteins
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Fungal Proteins
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I-kappa B Proteins
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NF-kappa B
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Nfkbia protein, mouse
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Schizosaccharomyces pombe Proteins
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NF-KappaB Inhibitor alpha
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Ubiquitin-Conjugating Enzymes
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Ligases
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HUS5 protein, S pombe
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ubiquitin-conjugating enzyme UBC9