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PNAS 106 (45): 18972-18977

Copyright © 2009 by the National Academy of Sciences.


BIOLOGICAL SCIENCES / BIOCHEMISTRY

Regulation of NF-{kappa}B activity through lysine monomethylation of p65

Chee-Kwee Ea David Baltimore1

Division of Biology, California Institute of Technology, 330 Braun, 1200 East California Boulevard, Pasadena, CA 91125

Contributed by David Baltimore, September 14, 2009

Received for publication July 31, 2009.

Abstract: NF-{kappa}B is a key activator of inflammatory and immune responses with important pathological roles in cancer, heart disease, and autoimmune diseases. Transcriptional activity of NF-{kappa}B is regulated by different posttranslational modifications. Here, we report a novel mechanism of NF-{kappa}B regulation through lysine monomethylation by SET9 methyltransferase. Set9 specifically methylates p65 at lysine 37. Both TNF{alpha} 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-{kappa}B target genes in response to TNF{alpha} stimulation.

Key Words: methylation • SET9


Freely available online through the PNAS open access option.

Author contributions: C.-K.E. and D.B. designed research; C.-K.E. performed research; C.-K.E. and D.B. analyzed data; and C.-K.E. and D.B. wrote the paper.

The authors declare no conflict of interest.

This article contains supporting information online at www.pnas.org/cgi/content/full/0910439106/DCSupplemental.

1To whom correspondence should be addressed. E-mail: baltimo{at}caltech.edu


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