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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

DC Field Value Language
dc.contributor.advisor백성희-
dc.contributor.author김동하-
dc.date.accessioned2018-05-28T17:09:41Z-
dc.date.available2018-05-28T17:09:41Z-
dc.date.issued2018-02-
dc.identifier.other000000149378-
dc.identifier.urihttps://hdl.handle.net/10371/141123-
dc.description학위논문 (박사)-- 서울대학교 대학원 : 자연과학대학 생명과학부, 2018. 2. 백성희.-
dc.description.abstractThe 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.-
dc.description.tableofcontentsCHAPTER I. Introduction 1
I-1. Lysine-specific demethylase 1 (LSD1) 2
1.1. Physiological functions of LSD1 2
1.2. Phosphorylation of LSD1 3
I-2. Protein kinase Cα (PKCα) 5
2.1. Structure of PKC family 5
2.2. Regulations of PKCα 6
I-3. Nuclear factor-kappa B (NF-κB) 8
3.1. Structure of NF-κB family 8
3.2. NF-κB signaling pathway 10
3.3. Physiological functions of NF-κB 11
I-4. Inflammation 13
4.1. The function of inflammation 13
4.2. Epigenetic and transcriptional regulation of inflammation 13
4.3. Septic Shock and Sepsis 14
CHAPTER II. LSD1 phosphorylation by PKCα is crucial for LPS-induced inflammatory responses 17
II-1. Summary 18
II-2. Introduction 19
II-3. Results 21
II-4. Discussion 42
II-5. Materials and Methods 45
CHAPTER III. Demethylation of p65 by LSD1 enhances protein stability of p65 55
III-1. Summary 56
III-2. Introduction 57
III-3. Results 59
III-4. Discussion 80
III-5. Materials and Methods 83
CHAPTER IV. Conclusion 96
REFERENCES 100
국문초록 / ABSTRACT IN KOREAN 119
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dc.formatapplication/pdf-
dc.format.extent7657415 bytes-
dc.format.mediumapplication/pdf-
dc.language.isoen-
dc.publisher서울대학교 대학원-
dc.subjectLysine-specific demethylase 1 (LSD1)-
dc.subjectProtein kinase Cα (PKCα)-
dc.subjectPhosphorylation-
dc.subjectEpigenetic regulation-
dc.subjectNuclear factor-kappa B (NF-κB)-
dc.subjectp65-
dc.subjectCCAAT-enhancer-binding proteins (C/EBPs)-
dc.subjectTranscription-
dc.subjectLipopolysaccharide (LPS)-
dc.subjectInflammation-
dc.subjectSepsis.-
dc.subject.ddc570-
dc.titleStudies on the Epigenetic and Transcriptional Regulation of LSD1 in Inflammatory Response-
dc.title.alternative염증 반응에서 LSD1의 후성 유전 및 전사 조절 기작에 대한 연구-
dc.typeThesis-
dc.contributor.AlternativeAuthorDongha Kim-
dc.description.degreeDoctor-
dc.contributor.affiliation자연과학대학 생명과학부-
dc.date.awarded2018-02-
Appears in Collections:
College of Natural Sciences (자연과학대학)Dept. of Biological Sciences (생명과학부)Theses (Ph.D. / Sc.D._생명과학부)
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