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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., 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 |
| ISSN: | 0305-1048 |
| Publisher: | Oxford University Press |
| Volume: | 26 |
| Number: | 7 |
| 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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