The inflammatory response mediated by NF-B signaling is essential for host defense against pathogens. Although the components and regulatory mechanism of NF-B signaling have been well-studied, molecular basis for the epigenetic regulation of the inflammatory response is poorly understood. Here, we identify a new signaling axis of PKC- LSD1-NF-B p65 which is critical for activation and amplification of the inflammatory response and triggering systemic inflammatory diseases. In response to excessive inflammatory stimuli, PKC translocates to the nucleus and phosphorylates LSD1. Phosphorylation of LSD1 is required for its interaction with p65 and facilitates demethylation of p65 leading to enhanced protein stability. Genome-wide analysis reveals a critical role of LPS-induced LSD1 phosphorylation in the transcriptional activation of NF-B target genes. Together, we demonstrate that PKC-LSD1-NF-B signaling cascade is crucial for epigenetic control of the inflammatory response. SOURCE: Dongha Kim (hidongha@gmail.com) -  Seoul National University

Pluto Bioinformatics

GSE100216: PKC-LSD1-NF-B Signaling Cascade Is Crucial for Epigenetic Control of the Inflammatory Response [RNA-Seq]