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Hsp90-Mediated Triage in the Glucocorticoid Receptor Life Cycle.
Hsp90-Mediated Triage in the Glucocorticoid Receptor Life Cycle.
상세정보
- 자료유형
- 학위논문
- Control Number
- 0017163496
- International Standard Book Number
- 9798384075752
- Dewey Decimal Classification Number
- 574
- Main Entry-Personal Name
- Chio, Tak Mei.
- Publication, Distribution, etc. (Imprint
- [S.l.] : University of California, San Francisco., 2024
- Publication, Distribution, etc. (Imprint
- Ann Arbor : ProQuest Dissertations & Theses, 2024
- Physical Description
- 105 p.
- General Note
- Source: Dissertations Abstracts International, Volume: 86-03, Section: B.
- General Note
- Advisor: Agard, David A.
- Dissertation Note
- Thesis (Ph.D.)--University of California, San Francisco, 2024.
- Summary, Etc.
- 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.
- Subject Added Entry-Topical Term
- Biochemistry.
- Subject Added Entry-Topical Term
- Cellular biology.
- Subject Added Entry-Topical Term
- Biology.
- Subject Added Entry-Topical Term
- Molecular biology.
- Index Term-Uncontrolled
- Ligase CHIP
- Index Term-Uncontrolled
- Degradation
- Index Term-Uncontrolled
- Glucocorticoid receptor
- Index Term-Uncontrolled
- Hsp90
- Index Term-Uncontrolled
- Structural biology
- Added Entry-Corporate Name
- University of California, San Francisco Chemistry and Chemical Biology
- Host Item Entry
- Dissertations Abstracts International. 86-03B.
- Electronic Location and Access
- 로그인을 한후 보실 수 있는 자료입니다.
- Control Number
- joongbu:655794
MARC
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■00520250211152715
■006m o d
■007cr#unu||||||||
■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[S.l.]▼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.
