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

ABSTRACT: Homeostatic regulation of NF-?B requires the continuous synthesis of I?B? and its rapid degradation by the proteasome through a ubiquitin-independent pathway. We previously showed that the ubiquitin-independent degradation signal of unbound I?B? 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 I?B?. 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 I?B?. 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 I?B?.

SUBMITTER: Mathes E 

PROVIDER: S-EPMC2963393 | biostudies-literature | 2010 Oct

REPOSITORIES: biostudies-literature