Cyclin-dependent kinase 6 phosphorylates NF-kappaB P65 at serine 536 and contributes to the regulation of inflammatory gene expression
dc.contributor.author | Buss, Holger | |
dc.contributor.author | Handschick, Katja | |
dc.contributor.author | Jurrmann, Nadine | |
dc.contributor.author | Pekkonen, Pirita | |
dc.contributor.author | Beuerlein, Knut | |
dc.contributor.author | Müller, Helmut | |
dc.contributor.author | Wait, Robin | |
dc.contributor.author | Saklatvala, Jeremy | |
dc.contributor.author | Ojala, Päivi M. | |
dc.contributor.author | Schmitz, M. Lienhard | |
dc.contributor.author | Naumann, Michael | |
dc.contributor.author | Kracht, Michael | |
dc.date.accessioned | 2022-11-18T09:57:06Z | |
dc.date.available | 2013-03-04T12:31:48Z | |
dc.date.available | 2022-11-18T09:57:06Z | |
dc.date.issued | 2012 | |
dc.description.abstract | Nuclear factor kappa-B (NF-kappaB) activates multiple genes with overlapping roles in cell proliferation, inflammation and cancer. Using an unbiased approach we identified human CDK6 as a novel kinase phosphorylating NF-kappaB p65 at serine 536. Purified and reconstituted CDK6/cyclin complexes phosphorylated p65 in vitro and in transfected cells. The physiological role of CDK6 for basal as well as cytokine-induced p65 phosphorylation or NF-?B activation was revealed upon RNAi-mediated suppression of CDK6. Inhibition of CDK6 catalytic activity by PD332991 suppressed activation of NF-?B and TNF-induced gene expression. In complex with a constitutively active viral cyclin CDK6 stimulated NF-?B p65-mediated transcription in a target gene specific manner and this effect was partially dependent on its ability to phosphorylate p65 at serine 536. Tumor formation in thymi and spleens of v-cyclin transgenic mice correlated with increased levels of p65 Ser536 phosphorylation, increased expression of CDK6 and upregulaton of the NF-?B target cyclin D3. These results suggest that aberrant CDK6 expression or activation that is frequently observed in human tumors can contribute through NF-?B to chronic inflammation and neoplasia. | en |
dc.identifier.uri | http://nbn-resolving.de/urn:nbn:de:hebis:26-opus-92322 | |
dc.identifier.uri | https://jlupub.ub.uni-giessen.de//handle/jlupub/9672 | |
dc.identifier.uri | http://dx.doi.org/10.22029/jlupub-9060 | |
dc.language.iso | en | de_DE |
dc.rights | Namensnennung 3.0 International | * |
dc.rights.uri | https://creativecommons.org/licenses/by/3.0/ | * |
dc.subject.ddc | ddc:610 | de_DE |
dc.title | Cyclin-dependent kinase 6 phosphorylates NF-kappaB P65 at serine 536 and contributes to the regulation of inflammatory gene expression | en |
dc.type | article | de_DE |
local.affiliation | FB 11 - Medizin | de_DE |
local.opus.fachgebiet | Medizin fachübergreifend | de_DE |
local.opus.id | 9232 | |
local.source.freetext | PLoS ONE 7(12):e51847; | de_DE |
local.source.uri | https://doi.org/10.1371/journal.pone.0051847 |
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