자료유형  

 학위논문

Control Number  

0017162680

International Standard Book Number  

9798384097525

Dewey Decimal Classification Number  

574

Main Entry-Personal Name  

Keenan, E. Keith.

Publication, Distribution, etc. (Imprint  

[S.l.] : Duke University., 2024

Publication, Distribution, etc. (Imprint  

Ann Arbor : ProQuest Dissertations & Theses, 2024

Physical Description  

128 p.

General Note  

Source: Dissertations Abstracts International, Volume: 86-03, Section: B.

General Note  

Includes supplementary digital materials.

General Note  

Advisor: Hirschey, Matthew;Newgard, Christopher.

Dissertation Note  

Thesis (Ph.D.)--Duke University, 2024.

Summary, Etc.  

요약Protein modifications modulate nearly every aspect of cell biology in organisms ranging from Archaea to Eukaryotes. The earliest evidence of covalent protein modifications was found in the early 20th century by studying the amino acid composition of proteins by chemical hydrolysis. These discoveries challenged what defined a canonical amino acid. The advent and rapid adoption of mass spectrometry-based proteomics in the latter part of the 20th century enabled a veritable explosion in the number of known protein modifications, with over 500 discrete modifications counted today. Now, new computational tools in data science, machine learning, and artificial intelligence are poised to allow researchers to make significant progress discovering new protein modifications and determining their function.Lysine acetylation is one of the most well-known post translational modifications. Acetylation is not limited to lysine with acetylation of serine and threonine having also been reported in the literature. Lysine acetylation is known to occur both enzymatically and non-enzymatically. Cysteine is a reactive amino acid central to the catalytic activities of many enzymes. Given the highly reactive nature of the cysteine side-chain, non-enzymatic acetylation of cysteine would be expected to be more favorable than non-enzymatic acetylation of lysine. Cysteine is also a common target of post-translational modifications (PTMs), such as palmitoylation. This long-chain acyl PTM can modify cysteine residues and induce changes in protein sub-cellular localization. Transfer of an acetyl moiety from the side-chain of cysteine to the side-chain of lysine has been shown in vitro. Cysteine side-chain acetylation has never been shown in vivo. We hypothesized that cysteine could also be modified by short-chain acyl groups, such as cysteine S-acetylation. To test this, we developed sample preparation and non-targeted mass spectrometry protocols to analyze the mouse liver proteome for cysteine acetylation. Our findings revealed hundreds of sites of cysteine acetylation across multiple tissue types, revealing a previously uncharacterized cysteine acetylome. The cysteine acetylome shows distinct patterns in different sub-cellular compartments and is most abundant in the cytoplasm. Cysteine acetylation is present in all tissue types tested and has tissue-specific acetylome patterns. Metabolic stress led to targeted changes in the cysteine acetylome of BAT. Acetylation of the active site cysteines of GAPDH led to a sharp reduction in activity. This study uncovers a novel aspect of cysteine biochemistry, highlighting short-chain modifications alongside known long-chain acyl PTMs. These findings enrich our understanding of the landscape of acyl modifications and suggest new research directions in enzyme activity regulation and cellular signaling in metabolism.

Subject Added Entry-Topical Term  

Molecular biology.

Subject Added Entry-Topical Term  

Biochemistry.

Subject Added Entry-Topical Term  

Cellular biology.

Subject Added Entry-Topical Term  

Oncology.

Index Term-Uncontrolled  

Cysteine acetylation

Index Term-Uncontrolled  

Metabolism

Index Term-Uncontrolled  

Post-translational modifications

Index Term-Uncontrolled  

Protein acetylation

Added Entry-Corporate Name  

Duke University Molecular Cancer Biology

Host Item Entry  

Dissertations Abstracts International. 86-03B.

Electronic Location and Access  

로그인을 한후 보실 수 있는 자료입니다.

Control Number  

joongbu:658168