Direct involvement of the ubiquitin-conjugating enzyme Ubc9/Hus5 in the degradation of IκBα
- 22 July 1997
- journal article
- research article
- Published by Proceedings of the National Academy of Sciences in Proceedings of the National Academy of Sciences
- Vol. 94 (15) , 7862-7867
- https://doi.org/10.1073/pnas.94.15.7862
Abstract
The NF-κB/Rel proteins are sequestered in the cytoplasm in association with IκBα. In response to external signals, IκBα is phosphorylated, multi-ubiquitinated, and degraded by proteasomes, thereby releasing NF-κB/Rel proteins to migrate to the nucleus. We have cloned a mouse ubiquitin-conjugating enzyme (mE2), which associates with IκBα. mE2 is homologous to the yeast Ubc9/Hus5 ubiquitin-conjugating enzyme. A transdominant-negative mutant of mE2 had no effect on phosphorylation of IκBα, but delayed its degradation. Correspondingly, tumor necrosis factor-α-inducible NF-κB activity was diminished. We propose that mE2 is directly involved in the ubiquitin conjugation of IκBα, a pivotal step in its degradation pathway.Keywords
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