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  Department of New Biology Theses Ph.D.

Investigation of deubiquitinating enzymes regulating TDP-43-induced proteinopathies

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dc.contributor.advisor 이병훈 -
dc.contributor.author Tran Non Nuoc -
dc.date.accessioned 2026-01-23T10:58:39Z -
dc.date.available 2026-01-23T10:58:39Z -
dc.date.issued 2025 -
dc.identifier.uri https://scholar.dgist.ac.kr/handle/20.500.11750/59760 -
dc.identifier.uri http://dgist.dcollection.net/common/orgView/200000888746 -
dc.description TDP-43, ubiquitin-proteasome system, deubiquitinating enzymes, proteinopathy -
dc.description.tableofcontents Chapter I. General introduction and background 1
1.1. TDP-43 proteinopathies 1
1.2. Characterization of TDP-43 structure and function 2
1.3. Pathological mechanisms of TDP-43 6
1.4. The importance of ubiquitination and deubiquitination events in quality control of TDP-43 and its fate decisions in TDP-43 proteinopathies 8
1.5. Objectives 14
Chapter II. Identification and characterization of DUBs regulating TDP-43 homeostasis 17
2.1. Identification of USP36 as a new regulator of TDP-43 turnover 17
2.1.1. Introduction 17
2.1.2. Doxycycline-inducible HA-tagged TDP-43 293 T-Rex cell line was generated 18
2.1.3. TDP-43 mutants have longer half-lives than the wild-type 19
2.1.4. The degradation of TDP-43 was in a UPS-dependent manner 19
2.1.5. Identification of USP36 as a DUB preventing TDP-43 degradation 21
2.1.6. USP36 colocalizes and interacts with TDP-43 22
2.1.7. Discussion 23
2.1.8. Future direction 24
2.2. USP5 controls the progression of TDP-43 neuronal toxicity 25
2.2.1. Introduction 25
2.2.2. USP5 regulates TDP-43 abundance in cells. 26
2.2.3. USP5 promotes phosphorylation and aggregation of TDP-43 in cells 28
2.2.4. USP5 augments cytoplasmic TDP-43 mislocalization 30
2.2.5. USP5 knockdown mitigates TDP-43-induced toxicity in vivo 32
2.2.6. Discussion 33
2.2.7. Future direction 34
Chapter Ⅲ. USP14 regulates TDP-43-induced proteinopathies by influencing its stability and localization 35
3.1. Introduction 35
3.2. Results 37
3.2.1. USP14 regulates TDP-43 degradation 37
3.2.2. Enhanced clearance by USP14 depletion reduces cytoplasmic TDP-43 mislocalzation 43
3.2.3. USP14 depletion alleviates TDP-43 toxicity in the cell and fly model 46
3.2.4. USP14 inhibition mitigates TDP-43 toxicity by reducing TDP-43 level 58
3.2.5. USP14 interacts with and deubiquitinates TDP-43 60
3.3. Discussion and conclusion 67
Chapter IV. Summary 73
Chapter V. Materials and methods 75
References 88
Summary in Korean 101		 -
dc.format.extent 101 -
dc.language eng -
dc.publisher DGIST -
dc.title Investigation of deubiquitinating enzymes regulating TDP-43-induced proteinopathies -
dc.title.alternative TDP-43 유도 단백질병증을 조절하는 탈유비퀴틴화 효소의 연구 -
dc.type Thesis -
dc.identifier.doi 10.22677/THESIS.200000888746 -
dc.description.degree Doctor -
dc.contributor.department Department of New Biology -
dc.contributor.coadvisor Young-Sam Lee -
dc.date.awarded 2025-08-01 -
dc.publisher.location Daegu -
dc.description.database dCollection -
dc.citation XT.ND T772 202508 -
dc.date.accepted 2025-07-21 -
dc.contributor.alternativeDepartment 뉴바이올로지학과 -
dc.subject.keyword TDP-43, ubiquitin-proteasome system, deubiquitinating enzymes, proteinopathy -
dc.contributor.affiliatedAuthor Tran Non Nuoc -
dc.contributor.affiliatedAuthor Byung-Hoon Lee -
dc.contributor.affiliatedAuthor Young-Sam Lee -
dc.contributor.alternativeName 트란 논눅 -
dc.contributor.alternativeName Byung-Hoon Lee -
dc.contributor.alternativeName 이영삼 -
dc.rights.embargoReleaseDate 2030-08-31 -
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