dc.contributor.author | Toruner, Murat | |
dc.contributor.author | Fernandez-Zapico, Martin | |
dc.contributor.author | Sha, Jing Jing | |
dc.contributor.author | Pham, Linh | |
dc.contributor.author | Urrutia, Raul | |
dc.contributor.author | Egan, Laurence J. | |
dc.date.accessioned | 2018-08-24T08:26:33Z | |
dc.date.available | 2018-08-24T08:26:33Z | |
dc.date.issued | 2006-01-05 | |
dc.identifier.citation | Toruner, Murat; Fernandez-Zapico, Martin; Sha, Jing Jing; Pham, Linh; Urrutia, Raul; Egan, Laurence J. (2006). Antianoikis effect of nuclear factor-κb through up-regulated expression of osteoprotegerin, bcl-2, and iap-1. Journal of Biological Chemistry 281 (13), 8686-8696 | |
dc.identifier.issn | 0021-9258,1083-351X | |
dc.identifier.uri | http://hdl.handle.net/10379/9939 | |
dc.description.abstract | Epithelial cells undergo a form of apoptosis termed anoikis when they lose extracellular attachments. We evaluated the role of transcription factor NF-kappa B in the regulation of anoikis susceptibility of intestinal epithelial cells. Culture of rat intestinal epithelial cells in suspension induced NF-kappa B activation, which blocked the anoikis of those cells, as assessed by internucleosomal DNA fragmentation and caspase-3 cleavage. Activation of NF-kappa B after the loss of extracellular attachments required focal adhesion kinase tyrosine 397 phosphorylation. This triggered a signaling cascade through phosphatidylinositol 3-kinase and AKT, to induce DNA binding of the RelA/p65 NF-kappa B polypeptide. NF-kappa B activated in this manner induced the up-regulated expression of a distinct program of genes that included osteoprotegerin, BCL-2, and IAP-1 ( inhibitor of apoptosis protein-1). Chromatin immunoprecipitation experiments revealed that NF-kappa B directly regulated the promoters of these 3 genes. Knock-down of the expression of osteoprotegerin, BCL-2, or inhibitor of apoptosis protein-1 by RNA interference showed that these factors inhibit anoikis, and genetic reconstitution of their expression alone or in combination restored normal levels of anoikis to NF-kappa B-inactive intestinal epithelial cells. Together, these findings have identified the molecular components of a previously unrecognized antianoikis pathway in intestinal epithelial cells. | |
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 | focal adhesion kinase | |
dc.subject | intestinal epithelial-cells | |
dc.subject | apoptosis-inducing ligand | |
dc.subject | ikk-beta | |
dc.subject | phosphatidylinositol 3-kinase | |
dc.subject | signaling pathway | |
dc.subject | cancer-cells | |
dc.subject | tnf-alpha | |
dc.subject | activation | |
dc.subject | survival | |
dc.title | Antianoikis effect of nuclear factor-κb through up-regulated expression of osteoprotegerin, bcl-2, and iap-1 | |
dc.type | Article | |
dc.identifier.doi | 10.1074/jbc.m512178200 | |
dc.local.publishedsource | http://www.jbc.org/content/281/13/8686.full.pdf | |
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