Asymmetric arginine dimethylation of RelA provides a repressive mark to modulate TNFα/NF-κB response

• DOI: 10.1073/pnas.1522372113
• Publication Date: 2016-04-06T03:03:19Z
• Authors: Anja Reintjes; Julian E. Fuchs; Leopold Kremser; Herbert H. Lindner; Klaus R. Liedl; Lukas A. Huber; Taras Valovka
• Keywords: Mice, Knockout; Protein-Arginine N-Methyltransferases; 0303 health sciences; Tumor Necrosis Factor-alpha; Transcription Factor RelA; NF-kappa B p50 Subunit; Molecular Dynamics Simulation; Arginine; Methylation; Cell Line; Repressor Proteins; Mice; 03 medical and health sciences; Animals; Humans; Signal Transduction

Significance The transcription factor nuclear factor kappa B (NF-κB) plays a vital role in cellular immune, stress, and proliferative responses by regulating genes. To maintain correct execution of the genetic program and to prevent pathologies (e.g., chronic inflammation), the activation of NF-κB has to be transient and precisely controlled. We describe a unique inhibitory mechanism that mediates NF-κB–dependent regulation of inflammation-associated genes and uses arginine methylation of the RelA subunit of NF-κB by protein arginine methyltransferase 1. This modification reduces the DNA-binding affinity of RelA, altering the recruitment to gene promoters and the transcriptional potency of NF-κB. This may be developed into an approach to inhibit the pathological functions of NF-κB.