NF-κB: Regulation by methylation

Tao Lu, George R. Stark

Research output: Contribution to journalArticle

38 Citations (Scopus)

Abstract

In normal cells exposed to stress, the central transcription factor NF-κB is activated only transiently, to modulate the activation of downstream immune responses. However, in most cancers, NFkB is abnormally activated constitutively, contributing thus to oncogenesis and tumor progression. Therefore, downregulating NF-κB activity is an important goal of cancer treatment. In order to control NF-κB activity therapeutically, it is helpful to understand the molecular mechanisms that normally govern its activation and how dysregulated NF-κB activity may aid the development of disease. Recent evidence from our laboratories and others indicates that, in addition to various posttranslational modifications of NF-κB that have been observed previously, including phosphorylation, ubiquitination, and acetylation, NF-κB can be methylated reversibly on lysine or arginine residues by histonemodifying enzymes, including lysine and arginine methyl transferases and demethylases. Furthermore, these methylations are required to activate many downstream genes. Interestingly, amplifications and mutations of several such enzymes have been linked to cancer. We propose that some of these mutations may alter the methylation not only of histones but also of NF-κB, making them attractive therapeutic targets.

Original languageEnglish
Pages (from-to)3692-3695
Number of pages4
JournalCancer Research
Volume75
Issue number18
DOIs
StatePublished - Sep 15 2015

Fingerprint

Methylation
Lysine
Arginine
Neoplasms
Mutation
Ubiquitination
Enzymes
Post Translational Protein Processing
Acetylation
Transferases
Histones
Carcinogenesis
Transcription Factors
Down-Regulation
Phosphorylation
Genes
Therapeutics

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

NF-κB : Regulation by methylation. / Lu, Tao; Stark, George R.

In: Cancer Research, Vol. 75, No. 18, 15.09.2015, p. 3692-3695.

Research output: Contribution to journalArticle

Lu, Tao ; Stark, George R. / NF-κB : Regulation by methylation. In: Cancer Research. 2015 ; Vol. 75, No. 18. pp. 3692-3695.
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