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J Biol Chem. 2010 Oct 22;285(43):32927-36. doi: 10.1074/jbc.M110.107326. Epub 2010 Aug 3.

Flexible regions within I{kappa}B{alpha} create the ubiquitin-independent degradation signal.

Author information

1
Department of Chemistry and Biochemistry, University of California, San Diego, La Jolla, California 92093, USA.

Abstract

Homeostatic regulation of NF-κB requires the continuous synthesis of IκBα and its rapid degradation by the proteasome through a ubiquitin-independent pathway. We previously showed that the ubiquitin-independent degradation signal of unbound IκBα was located in the C-terminal PEST region, and we have now identified a single tyrosine, Tyr-289, and determined that the hydrophobic character of the tyrosine is important for the rapid turnover of IκBα. The sequence composition of the PEST peptide surrounding this Tyr-289 imposes a distinct polyproline II conformation. Enhancing the polyproline II helix formation correlates with slower degradation rates of unbound IκBα. We have further identified a degradation signal located within the 5th ankyrin repeat that is functional once the C terminus is removed. Both the C-terminal and 5th ankyrin repeat degradation signals have inherent flexibility and specific hydrophobic residue(s), which together constitute the ubiquitin-independent degradation signal for IκBα.

PMID:
20682784
PMCID:
PMC2963393
DOI:
10.1074/jbc.M110.107326
[Indexed for MEDLINE]
Free PMC Article

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