SIGNAL-INDUCED DEGRADATION OF I-KAPPA-B-ALPHA - ASSOCIATION WITH NF-KAPPA-B AND THE PEST SEQUENCE IN I-KAPPA-B-ALPHA ARE NOT REQUIRED

Signal-induced degradation of I kappa B alpha via the ubiquitin-protea some pathway requires phosphorylation on residues serine 32 and serine 36 followed by ubiquitination on lysines 21 and 22. We investigated t he role of other regions of I kappa B alpha which may be involved in i ts degradation. Here we report that the carboxy-terminal PEST sequence is not required for I kappa B alpha signal-induced degradation. Howev er, removal of the PEST sequence stabilizes free I kappa B alpha in un stimulated cells. We further report that a PEST deletion mutant does n ot associate well with NF-kappa B proteins but is degraded in response to signal. Therefore, we conclude that both association with NF-kappa B and a PEST sequence are not required for signal-induced I kappa B a lpha degradation. Additionally, the PEST sequence may be required for constitutive turnover of free I kappa B alpha.