Role of novel serine 316 phosphorylation of the p65 subunit of NF-κB in differential gene regulation

Benlian Wang, Han Wei, Lakshmi Prabhu, Wei Zhao, Matthew Martin, Antja Voy Hartley, Tao Lu

Research output: Contribution to journalArticle

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Abstract

Nuclear 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.

Original languageEnglish
Pages (from-to)20336-20347
Number of pages12
JournalJournal of Biological Chemistry
Volume290
Issue number33
DOIs
StatePublished - Aug 14 2015

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Phosphorylation
Gene expression
Serine
Genes
Alanine
Neoplasms
Cell growth
Post Translational Protein Processing
Conditioned Culture Medium
Interleukin-1
Tumors
Carcinogenesis
Cells
Growth

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology
  • Molecular Biology

Cite this

Role of novel serine 316 phosphorylation of the p65 subunit of NF-κB in differential gene regulation. / Wang, Benlian; Wei, Han; Prabhu, Lakshmi; Zhao, Wei; Martin, Matthew; Hartley, Antja Voy; Lu, Tao.

In: Journal of Biological Chemistry, Vol. 290, No. 33, 14.08.2015, p. 20336-20347.

Research output: Contribution to journalArticle

Wang, Benlian ; Wei, Han ; Prabhu, Lakshmi ; Zhao, Wei ; Martin, Matthew ; Hartley, Antja Voy ; Lu, Tao. / Role of novel serine 316 phosphorylation of the p65 subunit of NF-κB in differential gene regulation. In: Journal of Biological Chemistry. 2015 ; Vol. 290, No. 33. pp. 20336-20347.
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