Role of Novel Serine 316 Phosphorylation of the p65 Subunit of NF-κB in Differential Gene Regulation

dc.contributor.authorWang, Benlian
dc.contributor.authorPrabhu, Lakshmi
dc.contributor.authorZhao, Wei
dc.contributor.authorMartin, Matthew
dc.contributor.authorHartley, Antja-Voy
dc.contributor.authorLu, Tao
dc.contributor.authorWei, Han
dc.contributor.departmentDepartment of Pharmacology and Toxicology, IU School of Medicineen_US
dc.date.accessioned2017-05-30T13:46:05Z
dc.date.available2017-05-30T13:46:05Z
dc.date.issued2015-06-16
dc.description.abstractNuclear factor κB (NF-κB) is a central coordinator in immune and inflammatory responses. Constitutive NF-κB is often found in some types of cancers, contributing to oncogenesis and tumor progression. Therefore, knowing how NF-κB is regulated is important for its therapeutic control. Post-translational modification of the p65 subunit of NF-κB is a well known approach for its regulation. Here, we reported that in response to interleukin 1β, the p65 subunit of NF-κB is phosphorylated on the novel serine 316. Overexpression of S316A (serine 316 → alanine) mutant exhibited significantly reduced ability to activate NF-κB and decreased cell growth as compared with wtp65 (wild type p65). Moreover, conditioned media from cells expressing the S316A-p65 mutant had a considerably lower ability to induce NF-κB than that of wtp65. Our data suggested that phosphorylation of p65 on Ser-316 controls the activity and function of NF-κB. Importantly, we found that phosphorylation at the novel Ser-316 site and other two known phosphorylation sites, Ser-529 and Ser-536, either individually or cooperatively, regulated distinct groups of NF-κB-dependent genes, suggesting the unique role of each individual phosphorylation site on NF-κB-dependent gene regulation. Our novel findings provide an important piece of evidence regarding differential regulation of NF-κB-dependent genes through phosphorylation of different p65 serine residues, thus shedding light on novel mechanisms for the pathway-specific control of NF-κB. This knowledge is key to develop strategies for prevention and treatment of constitutive NF-κB-driven inflammatory diseases and cancers.en_US
dc.identifier.citationWang, B., Wei, H., Prabhu, L., Zhao, W., Martin, M., Hartley, A.-V., & Lu, T. (2015). Role of Novel Serine 316 Phosphorylation of the p65 Subunit of NF-κB in Differential Gene Regulation. The Journal of Biological Chemistry, 290(33), 20336–20347. http://doi.org/10.1074/jbc.M115.639849en_US
dc.identifier.urihttps://hdl.handle.net/1805/12768
dc.language.isoen_USen_US
dc.publisherAmerican Society for Biochemistry & Molecular Biologyen_US
dc.relation.isversionof10.1074/jbc.M115.639849en_US
dc.relation.journalThe Journal of Biological Chemistryen_US
dc.rightsPublisher Policyen_US
dc.sourcePMCen_US
dc.subjectNF-κB (NF-κB)en_US
dc.subjectMass spectrometry (MS)en_US
dc.subjectPhosphorylationen_US
dc.subjectPost-translational modification (PTM)en_US
dc.subjectSerineen_US
dc.titleRole of Novel Serine 316 Phosphorylation of the p65 Subunit of NF-κB in Differential Gene Regulationen_US
dc.typeArticleen_US
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