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Thesis_ChunLunNi.pdf (5.94 MB)
ETD Abstract Container
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Polyglutamine Tract Expansion Increases Protein S-Nitrosylation and the Budding Yeast Zygote Transcriptome
Author Info
Ni, Chun-Lun
Permalink:
http://rave.ohiolink.edu/etdc/view?acc_num=case1481200808487517
Abstract Details
Year and Degree
2017, Doctor of Philosophy, Case Western Reserve University, Molecular Biology and Microbiology.
Abstract
This thesis describes two distinct projects in my graduate study: (A) The relationship between polyglutamine (polyQ) expansion and protein S-nitrosylation (Chapter 1-5). (B) Transcriptome remodeling during yeast zygote formation (Chapter 6). Chapter 1 describes the general background of Huntington’s diseases (HD), mutations of the Huntingtin protein (Htt), and the regulatory post-translational modifications (PTMs) of Htt. Chapter 2 specifically describes the current knowledge about regulations of S-nitrosylation and S-acylation on cysteine residues and their effects. Chapter 3 discusses our discovery that Htt S-nitrosylation is polyQ-dependent. We also observe a comparable polyQ expansion effect for Ataxin-1, another polyQ-containing protein whose polyQ expansion is pathogenic. Additionally, neither global S-nitrosylation nor normal Htt S-nitrosylation is increased in cells expressing polyQ-expanded Htt. Thus, polyQ expansion may regulate intramolecular S-nitrosylation. Mass spectrometry demonstrates that multiple sites are both S-nit rosylated and S-acylated in Htt. We test the effect of the C214S mutation on Htt S-nitrosylation and S-acylation because C214 was demonstrated to be a S-palmitoylation site. We find that this mutation significantly reduces S-nitrosylation and S-acylation in the context of normal polyQ but not for the expanded form. Therefore, polyQ expansion may regulate the profile of cysteine modifications within a protein molecule. In the Chapter 4, I discuss the interaction between nitric oxide synthases (NOSs) and Htt. We show that co-expression of Htt and NOS increases Htt inclusions in cultured cells. Nevertheless, co-immunoprecipitation experiments do not show markedly polyQ length-dependent Htt-NOS physical association. Chapter 5 first summarizes the results of this study, describes the computational simulation of HTT HEAT repeat motifs in cluster 1, and discusses the possible biological significance of S-nitrosylation regulated by polyglutamine tracts. We propose a simulated structure of the N-terminal fragment, based on the studies of other HEAT repeat structures and find that several S-nitrosylated and S-acylated cysteine residues are spatially clustered. Modifications of these cysteine residues therefore may be important for protein conformational changes and/or protein-protein interactions. In Chapter 6, I describe transcriptome analysis of budding yeast (S. cerevisiae) zygotes. For this purpose, we isolated zygotes and compared their transcriptomes to those of haploid cells, pheromone-stimulated haploid cells, and to diploid cells. We identified groups of genes that coincidentally increase or decrease in zygote via microarray analysis. These genes may imply the regulation of chromosome modulation and mitochondrial respiratory chain relevant to zygote physiology. This chapter is ended with the discussion and future directions for yeast zygote transcriptome study.
Committee
Alan Tartakoff, Ph.D. (Advisor)
Pages
201 p.
Subject Headings
Biochemistry
;
Biology
;
Cellular Biology
Keywords
HD
;
Htt
;
Ataxin1
;
polyglutamine
;
nitrosylation
;
nitric oxide synthase
;
HEAT repeat motif
;
budding yeast zygote
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Citations
Ni, C.-L. (2017).
Polyglutamine Tract Expansion Increases Protein S-Nitrosylation and the Budding Yeast Zygote Transcriptome
[Doctoral dissertation, Case Western Reserve University]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=case1481200808487517
APA Style (7th edition)
Ni, Chun-Lun.
Polyglutamine Tract Expansion Increases Protein S-Nitrosylation and the Budding Yeast Zygote Transcriptome.
2017. Case Western Reserve University, Doctoral dissertation.
OhioLINK Electronic Theses and Dissertations Center
, http://rave.ohiolink.edu/etdc/view?acc_num=case1481200808487517.
MLA Style (8th edition)
Ni, Chun-Lun. "Polyglutamine Tract Expansion Increases Protein S-Nitrosylation and the Budding Yeast Zygote Transcriptome." Doctoral dissertation, Case Western Reserve University, 2017. http://rave.ohiolink.edu/etdc/view?acc_num=case1481200808487517
Chicago Manual of Style (17th edition)
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Document number:
case1481200808487517
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1,154
Copyright Info
© 2016, some rights reserved.
Polyglutamine Tract Expansion Increases Protein S-Nitrosylation and the Budding Yeast Zygote Transcriptome by Chun-Lun Ni is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 3.0 Unported License. Based on a work at etd.ohiolink.edu.
This open access ETD is published by Case Western Reserve University School of Graduate Studies and OhioLINK.