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Articles 1 - 8 of 8
Full-Text Articles in Life Sciences
Chromatin Regulation By Rb-Interacting Proteins In Cellular Immune Functions, Seung June Kim
Chromatin Regulation By Rb-Interacting Proteins In Cellular Immune Functions, Seung June Kim
Electronic Thesis and Dissertation Repository
The retinoblastoma protein (RB) is historically known for its function in cell cycle control. However, mice carrying targeted Rb1 mutations have revealed that RB serves various non-cell cycle control roles. Notably, RB acts as a scaffold that recruits chromatin regulatory proteins, condensin II and enhancer of zeste homolog 2 (EZH2). These complexes protect the genome integrity through maintaining proper chromosome condensation, long range contacts, and transcriptionally repressive histone modification. This thesis explores the mechanistic links that regulate such RB-condensin II complex or that are leveraged upon pharmacological inhibition of the RB-EZH2 complex. First, I identified potential phosphorylation sites in the …
Probing The Genetic Code With Leucine Trna Variants, Peter Anderson Hall
Probing The Genetic Code With Leucine Trna Variants, Peter Anderson Hall
Electronic Thesis and Dissertation Repository
Mistranslation is an error in protein synthesis whereby the amino acids specified by the genetic code are misplaced by others in the growing polypeptide chain. The anticodon of tRNALeu can be altered allowing for the misincorporation of leucine at non-leucine codons. Observing the effect of tRNALeu variants on the viability of yeast and mammalian cells will provide information on their ability to cause mistranslation and potential relationship to genetic diseases. To explore this, a random pool of tRNALeu anticodonvariants was expressed in Saccharomyces cerevisiae. Furthermore, three mutant tRNALeu already sequenced from humans were expressed in …
Perseverance Of Protein Homeostasis Despite Mistranslation, Farah Hasan
Perseverance Of Protein Homeostasis Despite Mistranslation, Farah Hasan
Electronic Thesis and Dissertation Repository
Transfer RNAs (tRNAs) are essential for protein synthesis and translation fidelity. Some human tRNA variants may cause amino acid misincorporation: tRNAGly variants (tRNAGlyCCC, tRNAGlyGCC) have mutations that generate an alanine tRNA identity element (G3:U70), likely causing mis-aminoacylation of glycine tRNAs with alanine, while the tRNAAlaAGC G35C (tRNAAlaACC) variant may function similarly to mis-incorporate Ala at Gly codons by generating a Gly anticodon. I propose that these mistranslating tRNAs will disrupt protein homeostasis in mammalian cells. Although the tRNAGly and tRNAAla variants did not affect protein synthesis …
Tetr Family Regulator Farr Variation Controls Antimicrobial Fatty Acid Efflux In Staphylococcus Aureus, Camryn M. Bonn
Tetr Family Regulator Farr Variation Controls Antimicrobial Fatty Acid Efflux In Staphylococcus Aureus, Camryn M. Bonn
Electronic Thesis and Dissertation Repository
To colonize human skin and survive within abscesses, Staphylococcus aureus has evolved mechanisms to evade host innate defenses. USA300 has become the predominate community-acquired methicillin-resistant S. aureus (CA-MRSA) clone, which can be in part attributed to detoxification of unsaturated free fatty acids (uFFA) found in sebum and the nares. Our lab has previously identified the TetR family regulator FarR responsible for induction of the resistance-nodulation-division (RND) superfamily efflux pump FarE to promote efflux of toxic uFFA. However, RND family efflux pumps remain poorly characterized in Gram-positive species and the mechanism by which FarR regulates FarE has yet to be determined. …
The Expanding Roles Of Pacs-1 And Pacs-2 In Cellular Physiology: Beyond Vesicular Protein Trafficking, Rong Xuan Zang
The Expanding Roles Of Pacs-1 And Pacs-2 In Cellular Physiology: Beyond Vesicular Protein Trafficking, Rong Xuan Zang
Electronic Thesis and Dissertation Repository
Phosphofurin acidic cluster sorting (PACS) proteins 1 and 2 are essential components of the cytoplasmic protein trafficking machinery. Recent reports have described novel roles for PACS-1 in the nucleus. Here, we defined the mechanism of PACS-1 nucleocytoplasmic shuttling by identifying the interactions of PACS-1 with nuclear transport receptors and mapping its nuclear localization/export signals. Furthermore, we described the molecular basis and the subcellular location of the interactions between PACS-1 and RNA-binding proteins, including the cellular polypyrimidine tract-binding protein 1 and the HIV-1 Rev protein. In addition, we characterized the poorly understood biochemical properties of a PACS-2 E209K mutation involved in …
Characterizing The Transcriptome Of Sirt6-Deficient Aortic Smooth Muscle Cells, Ryan J. Wong
Characterizing The Transcriptome Of Sirt6-Deficient Aortic Smooth Muscle Cells, Ryan J. Wong
Electronic Thesis and Dissertation Repository
Several vascular diseases are marked by dysfunctional vascular smooth muscle cells (VSMCs). Our group has found that the knockout of the NAD+-dependent histone deacetylase sirtuin 6 (Sirt6), specifically in VSMCs, increases oxidative stress-induced DNA damage, inflammation, and aortic aneurysms in mice. To study the molecular mechanisms that drive VSMC dysfunction in Sirt6-deficiency, I established a primary culture model of Sirt6 deletion in VSMCs with Cre-lox technology. Through RNA sequencing of Sirt6-deficient VSMCs, we have identified modest but coordinated upregulations in transcripts involved in nucleosome assembly, inflammation, cell death, and autoimmunity. Immunostaining in histological sections of VSMC-specific …
The Sequence-Function Relationship Of Arabidopsis Arogenate Dehydratases, Emily J. Clayton
The Sequence-Function Relationship Of Arabidopsis Arogenate Dehydratases, Emily J. Clayton
Electronic Thesis and Dissertation Repository
Phenylalanine (Phe) is an essential aromatic amino acid that can only be synthesized de novo by microorganisms and plants. In microorganisms, Phe is synthesized through the prephenate pathway, requiring the activity of a prephenate dehydratase (PDT). In planta, Phe is synthesized instead through the arogenate pathway, requiring the enzyme arogenate dehydratase (ADT). In Arabidopsis, there is a family of six ADTs, named ADT1 through ADT6, that catalyze this step of Phe biosynthesis. All six AtADTs have a high sequence similarity and localize to the stromules of chloroplasts, the site of Phe biosynthesis in plants. Of note, two …
Illuminating Transfer Rna Variants As Genetic Modifiers In Models Of Human Disease, Jeremy T. Lant
Illuminating Transfer Rna Variants As Genetic Modifiers In Models Of Human Disease, Jeremy T. Lant
Electronic Thesis and Dissertation Repository
Transfer RNAs (tRNAs) physically link the genetic code to an amino acid sequence, by recruiting amino acids to three-nucleotide codons in messenger RNAs. To ensure that the genetic code is translated as intended, tRNAs must be accurately aminoacylated and faithfully recognize codons in the ribosome during protein synthesis. Given the critical function of tRNAs, it has often been assumed that mutations in human tRNA genes would be either lethal to cells or not significantly impair tRNA function. My goal was to rigorously test this assumption in mammalian cell models, prompted by the recent discovery of unprecedented variation in human tRNA …