| First Author | Dembinski HE | Year | 2017 |
| Journal | Proc Natl Acad Sci U S A | Volume | 114 |
| Issue | 8 | Pages | 1916-1921 |
| PubMed ID | 28167786 | Mgi Jnum | J:240921 |
| Mgi Id | MGI:5896840 | Doi | 10.1073/pnas.1610192114 |
| Citation | Dembinski HE, et al. (2017) Functional importance of stripping in NFkappaB signaling revealed by a stripping-impaired IkappaBalpha mutant. Proc Natl Acad Sci U S A 114(8):1916-1921 |
| abstractText | Stress-response transcription factors such as NFkappaB turn on hundreds of genes and must have a mechanism for rapid cessation of transcriptional activation. We recently showed that the inhibitor of NFkappaB signaling, IkappaBalpha, dramatically accelerates the dissociation of NFkappaB from transcription sites, a process we have called "stripping." To test the role of the IkappaBalpha C-terminal PEST (rich in proline, glutamic acid, serine, and threonine residues) sequence in NFkappaB stripping, a mutant IkappaBalpha was generated in which five acidic PEST residues were mutated to their neutral analogs. This IkappaBalpha(5xPEST) mutant was impaired in stripping NFkappaB from DNA and formed a more stable intermediate ternary complex than that formed from IkappaBalpha(WT) because DNA dissociated more slowly. NMR and amide hydrogen-deuterium exchange mass spectrometry showed that the IkappaBalpha(5xPEST) appears to be "caught in the act of stripping" because it is not yet completely in the folded and NFkappaB-bound state. When the mutant was introduced into cells, the rate of postinduction IkappaBalpha-mediated export of NFkappaB from the nucleus decreased markedly. |
