Regulation of NF-κB activity through lysine monomethylation of p65
Open Access
- 10 November 2009
- journal article
- research article
- Published by Proceedings of the National Academy of Sciences in Proceedings of the National Academy of Sciences of the United States of America
- Vol. 106 (45), 18972-18977
- https://doi.org/10.1073/pnas.0910439106
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
This publication has 25 references indexed in Scilit:
- Role of the Histone H3 Lysine 4 Methyltransferase, SET7/9, in the Regulation of NF-κB-dependent Inflammatory GenesPublished by Elsevier BV ,2008
- Regulation of Estrogen Receptor α by the SET7 Lysine MethyltransferaseMolecular Cell, 2008
- Ribosomal Protein S3: A KH Domain Subunit in NF-κB Complexes that Mediates Selective Gene RegulationCell, 2007
- Historical review: the field of protein methylationTrends in Biochemical Sciences, 2007
- Methylation of Lysine 4 on Histone H3: Intricacy of Writing and Reading a Single Epigenetic MarkMolecular Cell, 2007
- Repression of p53 activity by Smyd2-mediated methylationNature, 2006
- Post-translational modifications regulating the activity and function of the nuclear factor kappa B pathwayOncogene, 2006
- The key to development: interpreting the histone code?Current Opinion in Genetics & Development, 2005
- NF-κB AND REL PROTEINS: Evolutionarily Conserved Mediators of Immune ResponsesAnnual Review of Immunology, 1998
- Crystal structure of p50/p65 heterodimer of transcription factor NF-κB bound to DNANature, 1998