dc.contributor.author | Colleran, Amy | |
dc.contributor.author | Ryan, Aideen | |
dc.contributor.author | O'Gorman, Angela | |
dc.contributor.author | Mureau, Coralie | |
dc.contributor.author | Liptrot, Catherine | |
dc.contributor.author | Dockery, Peter | |
dc.contributor.author | Fearnhead, Howard | |
dc.contributor.author | Egan, Laurence J. | |
dc.date.accessioned | 2018-09-20T16:03:44Z | |
dc.date.available | 2018-09-20T16:03:44Z | |
dc.date.issued | 2011-03-31 | |
dc.identifier.citation | Colleran, Amy; Ryan, Aideen; O'Gorman, Angela; Mureau, Coralie; Liptrot, Catherine; Dockery, Peter; Fearnhead, Howard; Egan, Laurence J. (2011). Autophagosomal iκbα degradation plays a role in the long term control of tumor necrosis factor-α-induced nuclear factor-κb (nf-κb) activity. Journal of Biological Chemistry 286 (26), 22886-22893 | |
dc.identifier.issn | 0021-9258,1083-351X | |
dc.identifier.uri | http://hdl.handle.net/10379/10848 | |
dc.description.abstract | Transcription factor NF-kappa B is persistently activated in many chronic inflammatory diseases and cancers. The short term regulation of NF-kappa B is well understood, but little is known about the mechanisms of its long term activation. We studied the effect of a single application of TNF-alpha on NF-kappa B activity for up to 48 h in intestinal epithelial cells. Results show that NF-kappa B remained persistently activated up to 48 h after TNF-alpha and that the long term activation of NF-kappa B was accompanied by a biphasic degradation of I kappa B alpha. The first phase of I kappa B alpha degradation was proteasome-dependent, but the second was not. Further investigation showed that TNF-alpha stimulated formation of autophagosomes in intestinal epithelial cells and that I kappa B alpha co-localized with autophagosomal vesicles. Pharmacological or genetic blockade of autophagosome formation or the inhibition of lysosomal proteases decreased TNF-alpha-induced degradation of I kappa B alpha and lowered NF-kappa B target gene expression. Together, these findings indicate a role of autophagy in the control of long term NF-kappa B activity. Because abnormalities in autophagy have been linked to ineffective innate immunity, we propose that alterations in NF-kappa B may mediate this effect. | |
dc.publisher | American Society for Biochemistry & Molecular Biology (ASBMB) | |
dc.relation.ispartof | Journal of Biological Chemistry | |
dc.rights | Attribution-NonCommercial-NoDerivs 3.0 Ireland | |
dc.rights.uri | https://creativecommons.org/licenses/by-nc-nd/3.0/ie/ | |
dc.subject | inflammatory-bowel-disease | |
dc.subject | intestinal paneth cells | |
dc.subject | transcription factor | |
dc.subject | epithelial-cells | |
dc.subject | family-members | |
dc.subject | crohn-disease | |
dc.subject | activation | |
dc.subject | kinase | |
dc.subject | inhibitor | |
dc.subject | phosphorylation | |
dc.title | Autophagosomal iκbα degradation plays a role in the long term control of tumor necrosis factor-α-induced nuclear factor-κb (nf-κb) activity | |
dc.type | Article | |
dc.identifier.doi | 10.1074/jbc.m110.199950 | |
dc.local.publishedsource | http://www.jbc.org/content/286/26/22886.full.pdf | |
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