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Seryl-tRNA Synthetase in Translation and Cancer Inhibition
Seryl-tRNA Synthetase in Translation and Cancer Inhibition
상세정보
- 자료유형
- 학위논문 서양
- 최종처리일시
- 20250211151000
- ISBN
- 9798381972825
- DDC
- 574
- 저자명
- Wang, Justin.
- 서명/저자
- Seryl-tRNA Synthetase in Translation and Cancer Inhibition
- 발행사항
- [Sl] : The Scripps Research Institute, 2024
- 발행사항
- Ann Arbor : ProQuest Dissertations & Theses, 2024
- 형태사항
- 234 p
- 주기사항
- Source: Dissertations Abstracts International, Volume: 85-09, Section: B.
- 주기사항
- Advisor: Yang, Xiang-Lei.
- 학위논문주기
- Thesis (Ph.D.)--The Scripps Research Institute, 2024.
- 초록/해제
- 요약Aminoacyl-tRNA synthetases are essential gatekeepers of protein synthesis because of their conserved catalytic function of charging tRNAs with amino acids. The synthetases allowed direct translation of RNA code into protein, which enabled organisms to begin building complex cellular systems. While this catalytic function has stayed relatively constant, other aspects of the synthetases have changed dramatically throughout evolution. As life expanded into higher orders of organization, the aminoacyl-tRNA synthetases have changed by restructuring or adding new domains, many of which are dispensable for charging activity. These domains greatly diversified the interactomes of the synthetases beyond their usual ligands and interaction partners by providing surfaces for various other biomolecules to bind. Why? Two factors are the extreme selective pressure to maintain conditions for adequate protein synthesis and the ability of syntheses to sense energy (ATP), nutrient levels (amino acids), and translational state (tRNAs). tRNA synthetase research continually uncovers novel biological pathways and reveals how organisms adapted their proteomes to accommodate complexity. Here we demonstrate that seryl-tRNA synthetase cooperates with selenocysteine incorporation machinery to enable translational readthrough of stop codons on specific mRNAs to produce extended isoforms. The synthetases have repeatedly been linked to disease, including cancer, due to their prominence in homeostatic regulatory pathways. We demonstrate that each tRNA synthetase is unique, with individual expression profiles in cancer and unique profiles that resemble either tumor suppressors or oncogenes. We directly tested the effect of seryl-tRNA synthetase on cancer growth and metastasis, and we uncovered an inhibitory effect of the protein on both, potentially stemming from inhibitory effects on Wnt signaling. We also found evidence that SerRS influences cell migration and adhesion potentially through interactions with E-cadherin/catenin complexes.
- 일반주제명
- Molecular biology
- 일반주제명
- Cellular biology
- 일반주제명
- Biochemistry
- 키워드
- Beta-catenin
- 키워드
- E-cadherin
- 키워드
- Wnt signaling
- 기타저자
- The Scripps Research Institute Molecular Medicine
- 기본자료저록
- Dissertations Abstracts International. 85-09B.
- 전자적 위치 및 접속
- 로그인 후 원문을 볼 수 있습니다.
MARC
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■00520250211151000
■006m o d
■007cr#unu||||||||
■020 ▼a9798381972825
■035 ▼a(MiAaPQ)AAI30993860
■040 ▼aMiAaPQ▼cMiAaPQ
■0820 ▼a574
■1001 ▼aWang, Justin.
■24510▼aSeryl-tRNA Synthetase in Translation and Cancer Inhibition
■260 ▼a[Sl]▼bThe Scripps Research Institute▼c2024
■260 1▼aAnn Arbor▼bProQuest Dissertations & Theses▼c2024
■300 ▼a234 p
■500 ▼aSource: Dissertations Abstracts International, Volume: 85-09, Section: B.
■500 ▼aAdvisor: Yang, Xiang-Lei.
■5021 ▼aThesis (Ph.D.)--The Scripps Research Institute, 2024.
■520 ▼aAminoacyl-tRNA synthetases are essential gatekeepers of protein synthesis because of their conserved catalytic function of charging tRNAs with amino acids. The synthetases allowed direct translation of RNA code into protein, which enabled organisms to begin building complex cellular systems. While this catalytic function has stayed relatively constant, other aspects of the synthetases have changed dramatically throughout evolution. As life expanded into higher orders of organization, the aminoacyl-tRNA synthetases have changed by restructuring or adding new domains, many of which are dispensable for charging activity. These domains greatly diversified the interactomes of the synthetases beyond their usual ligands and interaction partners by providing surfaces for various other biomolecules to bind. Why? Two factors are the extreme selective pressure to maintain conditions for adequate protein synthesis and the ability of syntheses to sense energy (ATP), nutrient levels (amino acids), and translational state (tRNAs). tRNA synthetase research continually uncovers novel biological pathways and reveals how organisms adapted their proteomes to accommodate complexity. Here we demonstrate that seryl-tRNA synthetase cooperates with selenocysteine incorporation machinery to enable translational readthrough of stop codons on specific mRNAs to produce extended isoforms. The synthetases have repeatedly been linked to disease, including cancer, due to their prominence in homeostatic regulatory pathways. We demonstrate that each tRNA synthetase is unique, with individual expression profiles in cancer and unique profiles that resemble either tumor suppressors or oncogenes. We directly tested the effect of seryl-tRNA synthetase on cancer growth and metastasis, and we uncovered an inhibitory effect of the protein on both, potentially stemming from inhibitory effects on Wnt signaling. We also found evidence that SerRS influences cell migration and adhesion potentially through interactions with E-cadherin/catenin complexes.
■590 ▼aSchool code: 1179.
■650 4▼aMolecular biology
■650 4▼aCellular biology
■650 4▼aBiochemistry
■653 ▼aBeta-catenin
■653 ▼aCancer metastasis
■653 ▼aE-cadherin
■653 ▼aSeryl-tRNA synthetase
■653 ▼aTranslational readthrough
■653 ▼aWnt signaling
■690 ▼a0307
■690 ▼a0379
■690 ▼a0487
■71020▼aThe Scripps Research Institute▼bMolecular Medicine.
■7730 ▼tDissertations Abstracts International▼g85-09B.
■790 ▼a1179
■791 ▼aPh.D.
■792 ▼a2024
■793 ▼aEnglish
■85640▼uhttp://www.riss.kr/pdu/ddodLink.do?id=T17160339▼nKERIS▼z이 자료의 원문은 한국교육학술정보원에서 제공합니다.
