Regulation of NF-κB activity through lysine monomethylation of p65

Chee Kwee Ea, David Baltimore

Research output: Contribution to journalArticlepeer-review

192 Scopus citations


NF-κB is a key activator of inflammatory and immune responses with important pathological roles in cancer, heart disease, and autoimmune diseases. Transcriptional activity of NF-κB is regulated by different posttranslational modifications. Here, we report a novel mechanism of NF-κB regulation through lysine monomethylation by SET9 methyltransferase. Set9 specifically methylates p65 at lysine 37. Both TNFα and IL-1β treatments induced methylation of p65. Methylated p65 is restricted to the nucleus and this modification regulates the promoter binding of p65. Moreover, Set9 mediated methylation of p65 is required for the expression of a subset of NF-κB target genes in response to TNFα stimulation.

Original languageEnglish (US)
Pages (from-to)18972-18977
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Issue number45
StatePublished - Nov 10 2009


  • Methylation
  • SET9

ASJC Scopus subject areas

  • General


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