Cyclin-dependent kinase 6 phosphorylates NF-κB P65 at serine 536 and contributes to the regulation of inflammatory gene expression.
Nuclear factor kappa-B (NF-κB) 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-κB p65 at serine 536. Purified and reconstituted CDK6/cyclin complexes phosphorylate...
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2012
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oai:doaj.org-article:f0f07af112614169b2d732e1310cee772021-11-18T08:03:47ZCyclin-dependent kinase 6 phosphorylates NF-κB P65 at serine 536 and contributes to the regulation of inflammatory gene expression.1932-620310.1371/journal.pone.0051847https://doaj.org/article/f0f07af112614169b2d732e1310cee772012-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23300567/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203Nuclear factor kappa-B (NF-κB) 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-κB 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-κB activation was revealed upon RNAi-mediated suppression of CDK6. Inhibition of CDK6 catalytic activity by PD332991 suppressed activation of NF-κB and TNF-induced gene expression. In complex with a constitutively active viral cyclin CDK6 stimulated NF-κB 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-κB target cyclin D3. These results suggest that aberrant CDK6 expression or activation that is frequently observed in human tumors can contribute through NF-κB to chronic inflammation and neoplasia.Holger BussKatja HandschickNadine JurrmannPirita PekkonenKnut BeuerleinHelmut MüllerRobin WaitJeremy SaklatvalaPäivi M OjalaM Lienhard SchmitzMichael NaumannMichael KrachtPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 7, Iss 12, p e51847 (2012) |
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Medicine R Science Q Holger Buss Katja Handschick Nadine Jurrmann Pirita Pekkonen Knut Beuerlein Helmut Müller Robin Wait Jeremy Saklatvala Päivi M Ojala M Lienhard Schmitz Michael Naumann Michael Kracht Cyclin-dependent kinase 6 phosphorylates NF-κB P65 at serine 536 and contributes to the regulation of inflammatory gene expression. |
| description |
Nuclear factor kappa-B (NF-κB) 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-κB 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-κB activation was revealed upon RNAi-mediated suppression of CDK6. Inhibition of CDK6 catalytic activity by PD332991 suppressed activation of NF-κB and TNF-induced gene expression. In complex with a constitutively active viral cyclin CDK6 stimulated NF-κB 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-κB target cyclin D3. These results suggest that aberrant CDK6 expression or activation that is frequently observed in human tumors can contribute through NF-κB to chronic inflammation and neoplasia. |
| format |
article |
| author |
Holger Buss Katja Handschick Nadine Jurrmann Pirita Pekkonen Knut Beuerlein Helmut Müller Robin Wait Jeremy Saklatvala Päivi M Ojala M Lienhard Schmitz Michael Naumann Michael Kracht |
| author_facet |
Holger Buss Katja Handschick Nadine Jurrmann Pirita Pekkonen Knut Beuerlein Helmut Müller Robin Wait Jeremy Saklatvala Päivi M Ojala M Lienhard Schmitz Michael Naumann Michael Kracht |
| author_sort |
Holger Buss |
| title |
Cyclin-dependent kinase 6 phosphorylates NF-κB P65 at serine 536 and contributes to the regulation of inflammatory gene expression. |
| title_short |
Cyclin-dependent kinase 6 phosphorylates NF-κB P65 at serine 536 and contributes to the regulation of inflammatory gene expression. |
| title_full |
Cyclin-dependent kinase 6 phosphorylates NF-κB P65 at serine 536 and contributes to the regulation of inflammatory gene expression. |
| title_fullStr |
Cyclin-dependent kinase 6 phosphorylates NF-κB P65 at serine 536 and contributes to the regulation of inflammatory gene expression. |
| title_full_unstemmed |
Cyclin-dependent kinase 6 phosphorylates NF-κB P65 at serine 536 and contributes to the regulation of inflammatory gene expression. |
| title_sort |
cyclin-dependent kinase 6 phosphorylates nf-κb p65 at serine 536 and contributes to the regulation of inflammatory gene expression. |
| publisher |
Public Library of Science (PLoS) |
| publishDate |
2012 |
| url |
https://doaj.org/article/f0f07af112614169b2d732e1310cee77 |
| work_keys_str_mv |
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| _version_ |
1718422390003728384 |