Journal
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Volume 106, Issue 45, Pages 18972-18977Publisher
NATL ACAD SCIENCES
DOI: 10.1073/pnas.0910439106
Keywords
methylation; SET9
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Funding
- NIGMS NIH HHS [R01 GM039458, R01 GM039458-24] Funding Source: Medline
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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-1 beta 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.
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