Regulation of NF-κB activity through lysine monomethylation of p65

Chee Kwee Ea, David Baltimore

Research output: Contribution to journalArticle

150 Citations (Scopus)

Abstract

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
Volume106
Issue number45
DOIs
StatePublished - Nov 10 2009

Fingerprint

Methylation
Lysine
Methyltransferases
Post Translational Protein Processing
Interleukin-1
Autoimmune Diseases
Heart Diseases
Genes
Neoplasms

Keywords

  • Methylation
  • SET9

ASJC Scopus subject areas

  • General

Cite this

Regulation of NF-κB activity through lysine monomethylation of p65. / Ea, Chee Kwee; Baltimore, David.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 106, No. 45, 10.11.2009, p. 18972-18977.

Research output: Contribution to journalArticle

@article{ab417d2baf7a456791636e0b25590151,
title = "Regulation of NF-κB activity through lysine monomethylation of p65",
abstract = "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.",
keywords = "Methylation, SET9",
author = "Ea, {Chee Kwee} and David Baltimore",
year = "2009",
month = "11",
day = "10",
doi = "10.1073/pnas.0910439106",
language = "English (US)",
volume = "106",
pages = "18972--18977",
journal = "Proceedings of the National Academy of Sciences of the United States of America",
issn = "0027-8424",
number = "45",

}

TY - JOUR

T1 - Regulation of NF-κB activity through lysine monomethylation of p65

AU - Ea, Chee Kwee

AU - Baltimore, David

PY - 2009/11/10

Y1 - 2009/11/10

N2 - 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.

AB - 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.

KW - Methylation

KW - SET9

UR - http://www.scopus.com/inward/record.url?scp=73149099403&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=73149099403&partnerID=8YFLogxK

U2 - 10.1073/pnas.0910439106

DO - 10.1073/pnas.0910439106

M3 - Article

C2 - 19864627

AN - SCOPUS:73149099403

VL - 106

SP - 18972

EP - 18977

JO - Proceedings of the National Academy of Sciences of the United States of America

JF - Proceedings of the National Academy of Sciences of the United States of America

SN - 0027-8424

IS - 45

ER -