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Studies on the Epigenetic and Transcriptional Regulation of LSD1 in Inflammatory Response
염증 반응에서 LSD1의 후성 유전 및 전사 조절 기작에 대한 연구

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Authors
김동하
Advisor
백성희
Major
자연과학대학 생명과학부
Issue Date
2018-02
Publisher
서울대학교 대학원
Keywords
Lysine-specific demethylase 1 (LSD1)Protein kinase Cα (PKCα)PhosphorylationEpigenetic regulationNuclear factor-kappa B (NF-κB)p65CCAAT-enhancer-binding proteins (C/EBPs)TranscriptionLipopolysaccharide (LPS)InflammationSepsis.
Description
학위논문 (박사)-- 서울대학교 대학원 : 자연과학대학 생명과학부, 2018. 2. 백성희.
Abstract
The inflammatory response is an essential host defense mechanism against invading pathogens. NF-κB signaling plays a key role in regulating the inflammatory response, and misregulation of NF-κB signaling is involved in cancer and autoimmune disease. Although protein kinase C (PKC) signaling is shown to be crucial for the activation of the inflammatory response, the molecular mechanism of activation of the inflammatory response by PKC remains unclear. Here, I find that PKCα is translocated into the nucleus in response to inflammatory signal and directly phosphorylates lysine specific demethylase 1 (LSD1) in the nucleus. Lipopolysaccharide (LPS)-induced LSD1 phosphorylation by PKCα is required for its interaction with p65, and phosphorylated LSD1 facilitates demethylation of p65 leading to enhanced p65 protein stability. Genome-wide analysis reveals that LPS-induced LSD1 phosphorylation leads to activation of NF-κB target genes involved in sepsis. Importantly, Lsd1SA/SA mice with ablation of LSD1 phosphorylation show attenuated LPS-induced lung inflammatory injury and sepsis-induced mortality with greater survival rates than wild-type (WT) mice. Together, our data indicate that targeting PKCα signaling with its downstream LSD1 could be potentially powerful therapeutic strategy for inflammatory diseases such as sepsis.
Language
English
URI
https://hdl.handle.net/10371/141123
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College of Natural Sciences (자연과학대학)Dept. of Biological Sciences (생명과학부)Theses (Ph.D. / Sc.D._생명과학부)
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