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Signal-dependent degradation of IkappaBalpha is mediated by an inducible destruction box that can be transferred to NF-kappaB, bcl-3 or p53

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Item Type:Article
Title:Signal-dependent degradation of IkappaBalpha is mediated by an inducible destruction box that can be transferred to NF-kappaB, bcl-3 or p53
Creators Name:Wulczyn, F.G. and Krappmann, D. and Scheidereit, C.
Abstract:Activation of the transcription factor NF-kappaB in response to a variety of stimuli is governed by the signal-induced proteolytic degradation of NF-kappaB inhibitor proteins, the IkappaBs. We have investigated the sequence requirements for signal-induced IkappaBalpha phosphorylation and proteolysis by generating chimeric proteins containing discrete sub-regions of IkappaBalpha fused to the IkappaBalpha homologue Bcl-3, the transcription factor NF-kappaB1/p50 and the tumour suppressor protein p53. Using this approach we show that the N-terminal signal response domain (SRD) of IkappaBalpha directs their signal-dependent phosphorylation and degradation when transferred to heterologous proteins. The C-terminal PEST sequence from IkappaBalpha was not essential for induced proteolysis of the chimeric proteins. A deletion analysis conducted on the SRD identified a 25 amino acid sub-domain of IkappaBalpha that is necessary and sufficient for the degradative response in vivo and for recognition by TNFalpha-dependent IkappaBalpha kinase in vitro . The results obtained should prove instrumental in the further characterization of IkappaB-specific kinases, as well as the E2 and E3 enzymes responsible for IkappaBalpha ubiquitination. Furthermore, they suggest a novel strategy for generating conditional mutants, by targetting heterologous proteins for transient elimination by the IkappaBalpha pathway.
Keywords:Amino Acid Sequence, Amino Acid Sequence Homology, Base Sequence, DNA Primers, DNA-Binding Proteins, HeLa Cells, I-kappa B Proteins, Molecular Sequence Data, NF-kappa B, Open Reading Frames, Phosphorylation, Polymerase Chain Reaction, Proto-Oncogene Proteins, Recombinant Proteins, Sequence Alignment, Transcription Factors, Tumor Suppressor Protein p53
Source:Nucleic Acids Research
Publisher:Oxford University Press
Page Range:1724-1730
Date:1 April 1998
Official Publication:http://nar.oxfordjournals.org/cgi/content/abstract/26/7/1724
PubMed:View item in PubMed

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