dc.contributor.author | Song, L | |
dc.contributor.author | Li, J | |
dc.contributor.author | Zhang, D | |
dc.contributor.author | Liu, ZG | |
dc.contributor.author | Ye, J | |
dc.contributor.author | Zhan, Q | |
dc.contributor.author | Shen, HM | |
dc.contributor.author | Whiteman, Matthew | |
dc.contributor.author | Huang, C | |
dc.date.accessioned | 2015-04-14T09:04:50Z | |
dc.date.issued | 2006-11-20 | |
dc.description.abstract | Cross talk between NF-kappaB and c-Jun N-terminal kinases (JNKs) has been implicated in the cell life and death decision under various stresses. Functional suppression of JNK activation by NF-kappaB has recently been proposed as a key cellular survival mechanism and contributes to cancer cells escaping from apoptosis. We provide a novel scenario of the proapoptotic role of IkappaB kinase beta (IKKbeta)-NF-kappaB, which can act as the activator of the JNK pathway through the induction of GADD45alpha for triggering MKK4/JNK activation, in response to the stimulation of arsenite, a cancer therapeutic reagent. This effect of IKKbeta-NF-kappaB is dependent on p50 but not the p65/relA NF-kappaB subunit, which can increase the stability of GADD45alpha protein through suppressing its ubiquitination and proteasome-dependent degradation. IKKbeta-NF-kappaB can therefore either activate or suppress the JNK cascade and consequently mediate pro- or antiapoptotic effects, depending on the manner of its induction. Furthermore, the NF-kappaB p50 subunit can exert a novel regulatory function on protein modification independent of the classical NF-kappaB transcriptional activity. | en_GB |
dc.description.sponsorship | National Institutes of Health/National Cancer Institute | en_GB |
dc.description.sponsorship | National Institutes of Health/National Institute of Environmental Health Sciences | en_GB |
dc.identifier.citation | Vol. 175, pp. 607 - 617 | en_GB |
dc.identifier.doi | 10.1083/jcb.200602149 | |
dc.identifier.grantnumber | CA094964, CA112557, and CA103180 | en_GB |
dc.identifier.grantnumber | ES012451 and ES000260 | en_GB |
dc.identifier.uri | http://hdl.handle.net/10871/16776 | |
dc.language.iso | en | en_GB |
dc.publisher | Rockefeller University Press | en_GB |
dc.relation.url | http://www.ncbi.nlm.nih.gov/pubmed/17116751 | en_GB |
dc.rights | © 2006 Rockefeller University Press | en_GB |
dc.subject | Animals | en_GB |
dc.subject | Apoptosis | en_GB |
dc.subject | Arsenites | en_GB |
dc.subject | Cell Cycle Proteins | en_GB |
dc.subject | Enzyme Activation | en_GB |
dc.subject | Fibroblasts | en_GB |
dc.subject | I-kappa B Kinase | en_GB |
dc.subject | JNK Mitogen-Activated Protein Kinases | en_GB |
dc.subject | MAP Kinase Kinase 4 | en_GB |
dc.subject | Mice | en_GB |
dc.subject | NF-kappa B p50 Subunit | en_GB |
dc.subject | Nuclear Proteins | en_GB |
dc.subject | Phosphorylation | en_GB |
dc.subject | Proteasome Endopeptidase Complex | en_GB |
dc.subject | Protein Processing, Post-Translational | en_GB |
dc.subject | Signal Transduction | en_GB |
dc.subject | Transcription Factor RelA | en_GB |
dc.subject | Ubiquitin | en_GB |
dc.subject | Up-Regulation | en_GB |
dc.title | IKKbeta programs to turn on the GADD45alpha-MKK4-JNK apoptotic cascade specifically via p50 NF-kappaB in arsenite response | en_GB |
dc.type | Article | en_GB |
dc.date.available | 2015-04-14T09:04:50Z | |
dc.identifier.issn | 0021-9525 | |
exeter.place-of-publication | United States | |
dc.identifier.journal | Journal of Cell Biology | en_GB |