Open AccessSignal-Induced Degradation of IκBα: Association with NF-κB and the PEST Sequence in IκBα Are Not Required
Author(s) -
Daniel J. Van Antwerp,
Inder M. Verma
Publication year - 1996
Publication title -
molecular and cellular biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.14
H-Index - 327
eISSN - 1067-8824
pISSN - 0270-7306
DOI - 10.1128/mcb.16.11.6037
Subject(s) - biology , serine , ubiquitin , degradation (telecommunications) , pest analysis , kappa , phosphorylation , alpha (finance) , proteasome , sequence (biology) , biochemistry , microbiology and biotechnology , botany , medicine , gene , telecommunications , linguistics , philosophy , construct validity , nursing , computer science , patient satisfaction
Signal-induced degradation of I(kappa)B(alpha) via the ubiquitin-proteasome pathway requires phosphorylation on residues serine 32 and serine 36 followed by ubiquitination on lysines 21 and 22. We investigated the role of other regions of I(kappa)B(alpha) which may be involved in its degradation. Here we report that the carboxy-terminal PEST sequence is not required for I(kappa)B(alpha) signal-induced degradation. However, removal of the PEST sequence stabilizes free I(kappa)B(alpha) in unstimulated cells. We further report that a PEST deletion mutant does not 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(alpha) degradation. Additionally, the PEST sequence may be required for constitutive turnover of free I(kappa)B(alpha).