Hsp90-Mediated Triage in the Glucocorticoid Receptor Life Cycle
Hsp90-Mediated Triage in the Glucocorticoid Receptor Life Cycle
상세정보
- 자료유형
- 학위논문 서양
- 최종처리일시
- 20250211152715
- ISBN
- 9798384075752
- DDC
- 574
- 저자명
- Chio, Tak Mei.
- 서명/저자
- Hsp90-Mediated Triage in the Glucocorticoid Receptor Life Cycle
- 발행사항
- [Sl] : University of California, San Francisco, 2024
- 발행사항
- Ann Arbor : ProQuest Dissertations & Theses, 2024
- 형태사항
- 105 p
- 주기사항
- Source: Dissertations Abstracts International, Volume: 86-03, Section: B.
- 주기사항
- Advisor: Agard, David A.
- 학위논문주기
- Thesis (Ph.D.)--University of California, San Francisco, 2024.
- 초록/해제
- 요약The molecular chaperone Hsp90 is required for the folding of approximately 10% of our cellular proteome (so-called "client" proteins) throughout their lifetime in the cell. In addition to its protein folding activity, Hsp90 guards proteome integrity by promoting the degradation of misfolded proteins. Yet while Hsp90's folding function is delineated in increasing mechanistic detail, it remains unclear how Hsp90 targets a protein for degradation, for example, via presentation to an E3 ubiquitin ligase. To elucidate how Hsp90 can simultaneously effect both folding and degradation outcomes and in this way mediate protein-triage decisions, we have been pursuing approaches in structure/cryo-electron microscopy and biochemistry in the context of a model Hsp90 client, the glucocorticoid receptor (GR). Efforts and results are described in Chapter 4. Chapter 1 provides an introduction to Hsp90 and its connection to protein degradation. Chapter 2 details the design and validation of a mammalian reporter cell line for a pooled CRISPRi screen to discover Hsp90-dependent E3 ubiquitin ligases mediating the degradation of GR. Chapter 3 details efforts to reconstitute the chaperone cycle for another Hsp90 client, the cystic fibrosis transmembrane conductance regulator (CFTR), in the hopes that CFTR's degradation as induced by the E3 ligase CHIP could be explored.
- 일반주제명
- Biochemistry
- 일반주제명
- Cellular biology
- 일반주제명
- Biology
- 일반주제명
- Molecular biology
- 키워드
- Ligase CHIP
- 키워드
- Degradation
- 키워드
- Hsp90
- 기타저자
- University of California, San Francisco Chemistry and Chemical Biology
- 기본자료저록
- Dissertations Abstracts International. 86-03B.
- 전자적 위치 및 접속
- 로그인 후 원문을 볼 수 있습니다.
MARC
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■006m o d
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■020 ▼a9798384075752
■035 ▼a(MiAaPQ)AAI31489051
■040 ▼aMiAaPQ▼cMiAaPQ
■0820 ▼a574
■1001 ▼aChio, Tak Mei.▼0(orcid)0000-0001-8381-1957
■24510▼aHsp90-Mediated Triage in the Glucocorticoid Receptor Life Cycle
■260 ▼a[Sl]▼bUniversity of California, San Francisco▼c2024
■260 1▼aAnn Arbor▼bProQuest Dissertations & Theses▼c2024
■300 ▼a105 p
■500 ▼aSource: Dissertations Abstracts International, Volume: 86-03, Section: B.
■500 ▼aAdvisor: Agard, David A.
■5021 ▼aThesis (Ph.D.)--University of California, San Francisco, 2024.
■520 ▼aThe molecular chaperone Hsp90 is required for the folding of approximately 10% of our cellular proteome (so-called "client" proteins) throughout their lifetime in the cell. In addition to its protein folding activity, Hsp90 guards proteome integrity by promoting the degradation of misfolded proteins. Yet while Hsp90's folding function is delineated in increasing mechanistic detail, it remains unclear how Hsp90 targets a protein for degradation, for example, via presentation to an E3 ubiquitin ligase. To elucidate how Hsp90 can simultaneously effect both folding and degradation outcomes and in this way mediate protein-triage decisions, we have been pursuing approaches in structure/cryo-electron microscopy and biochemistry in the context of a model Hsp90 client, the glucocorticoid receptor (GR). Efforts and results are described in Chapter 4. Chapter 1 provides an introduction to Hsp90 and its connection to protein degradation. Chapter 2 details the design and validation of a mammalian reporter cell line for a pooled CRISPRi screen to discover Hsp90-dependent E3 ubiquitin ligases mediating the degradation of GR. Chapter 3 details efforts to reconstitute the chaperone cycle for another Hsp90 client, the cystic fibrosis transmembrane conductance regulator (CFTR), in the hopes that CFTR's degradation as induced by the E3 ligase CHIP could be explored.
■590 ▼aSchool code: 0034.
■650 4▼aBiochemistry
■650 4▼aCellular biology
■650 4▼aBiology
■650 4▼aMolecular biology
■653 ▼aLigase CHIP
■653 ▼aDegradation
■653 ▼aGlucocorticoid receptor
■653 ▼aHsp90
■653 ▼aStructural biology
■690 ▼a0487
■690 ▼a0379
■690 ▼a0306
■690 ▼a0307
■71020▼aUniversity of California, San Francisco▼bChemistry and Chemical Biology.
■7730 ▼tDissertations Abstracts International▼g86-03B.
■790 ▼a0034
■791 ▼aPh.D.
■792 ▼a2024
■793 ▼aEnglish
■85640▼uhttp://www.riss.kr/pdu/ddodLink.do?id=T17163496▼nKERIS▼z이 자료의 원문은 한국교육학술정보원에서 제공합니다.
