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Full-Text Articles in Biochemistry, Biophysics, and Structural Biology

Knocking Out A Negative Regulator Of Hedgehog Signaling Blocks Differentiation Of Cells Into Neurons, Danielle Margaret Spice, Gregory M. Kelly Ph.D. Jun 2019

Knocking Out A Negative Regulator Of Hedgehog Signaling Blocks Differentiation Of Cells Into Neurons, Danielle Margaret Spice, Gregory M. Kelly Ph.D.

Western Research Forum

Hedgehog (Hh) signaling, one of many different protein signaling pathways found in mammals, is vital in many stage of neural development. A major negative regulator of Hh signaling is a protein known as Suppressor of Fused (SUFU), which acts to sequester the full length Gli transcription factors, proteins that can turn genes on and off, in the cytoplasm or facilitates its conversion to a repressive form. The P19 embryonal carcinoma cell line is a model of hind-brain neuronal differentiation and the involvement of Hh signaling, in particular the role of SUFU in this process has yet to be explored. We ...


The 2Β Insert Perturbs Folding, Stability And Hydrophobic Exposure Of Stromal Interaction Molecules, Steve Chung Oct 2018

The 2Β Insert Perturbs Folding, Stability And Hydrophobic Exposure Of Stromal Interaction Molecules, Steve Chung

Electronic Thesis and Dissertation Repository

Stromal interaction molecule (STIM)1 and 2 regulate agonist-induced and basal cytosolic calcium (Ca2+) levels through oligomerization and translocation to endoplasmic reticulum (ER)-plasma membrane (PM) junctions. At these junctions, the STIM cytosolic coiled-coil domains couple to PM Orai1 protein subunits to form Ca2+ released activated Ca2+ (CRAC) channels that facilitate store-operated Ca2+ entry (SOCE). One splice variant of STIM2, STIM2β, contains an extra 8-residue (2β insert) located within the coiled-coils and inhibits SOCE through an unresolved mechanism, adding another layer of complexity to Ca2+ regulation in mammals. I hypothesize that the 2β insert perturbs the coiled-coil conformation and dynamics ...


Characterization Of Interleukin (Il)-1Β Regulatory Elements And Chromatin Conformation In Macrophage Activation, Woohyun Cho Aug 2018

Characterization Of Interleukin (Il)-1Β Regulatory Elements And Chromatin Conformation In Macrophage Activation, Woohyun Cho

Electronic Thesis and Dissertation Repository

IL-1β is a potent inflammatory cytokine promptly expressed in activated myeloid cells. PU.1 is a lineage-determining transcription factor that regulates myeloid-specific genes by activating distal enhancers. This study addresses the functional importance of a potential enhancer of IL-1β, and how PU.1 regulates its activity state. A putative enhancer RNA (eRNA) was transcribed from the enhancer, and eRNA knock-down with antisense oligonucleotides inhibited IL-1β production. Furthermore, enhancer-promoter interactions in stimulated macrophages were detected via chromatin conformation capture (3C) analysis. The role of PU.1 was examined in PU.1-overexpressed B16-BL6 cells, which responded to LPS and expressed IL-1β mRNA ...


Production Of A Candidate Recombinant Protein Vaccine For Mannheimia Haemolytica In Lettuce And Tobacco Chloroplasts, Coby K. Martin Jul 2018

Production Of A Candidate Recombinant Protein Vaccine For Mannheimia Haemolytica In Lettuce And Tobacco Chloroplasts, Coby K. Martin

Electronic Thesis and Dissertation Repository

The cattle industry worldwide is ravaged by bovine respiratory disease (BRD), a bacterial disease caused by Mannheimia haemolytica. Recent efforts to design vaccines against M. haemolytica focus on a virulence factor, leukotoxin, in addition to surface lipoproteins. Plant-based protein production is a safe and inexpensive alternative to traditional methods. Edible vaccines deliver antigens to pharyngeal tissues, which can provide local immunization against M. haemolytica prior to its progression into the lungs. In this project, a chimeric protein containing M. haemolytica antigens was produced in tobacco chloroplasts as a candidate edible vaccine for BRD. Attempts were made to transform lettuce chloroplasts ...


Defective Aba-Mediated Sugar Signalling Pathway In An Established Arabidopsis Thaliana Cell Suspension Culture Explains Its Stay-Green Phenotype At High Sugar Concentrations, Avery Mccarthy Jun 2018

Defective Aba-Mediated Sugar Signalling Pathway In An Established Arabidopsis Thaliana Cell Suspension Culture Explains Its Stay-Green Phenotype At High Sugar Concentrations, Avery Mccarthy

Electronic Thesis and Dissertation Repository

An unusual sugar insensitive phenotype was identified in an established cell suspension culture of Arabidopsis thaliana. We characterized the physiology, biochemistry and genetics of the sugar insensitive cell culture, in order to identify factors contributing to the phenotype. Chlorophyll levels of the cell suspension culture were insensitive to high sucrose (6-15% w/v) and maintained a green phenotype. Immunoblotting indicated that levels of key photosynthetic proteins (PsaA, Lhcb2 and Rubisco) increased as a function of external sucrose concentration. The green cell culture was photosynthetically competent based on light-dependent, CO2-saturated rates of O2 evolution as well as Fv ...


Role Of Pu.1 And C/Ebpα In Remodelling The Interleukin (Il)-1Β Enhancer-Promoter Interaction, Woohyun Cho, Soon-Duck Ha, Sung Ouk Kim Mar 2018

Role Of Pu.1 And C/Ebpα In Remodelling The Interleukin (Il)-1Β Enhancer-Promoter Interaction, Woohyun Cho, Soon-Duck Ha, Sung Ouk Kim

Western Research Forum

Background: IL-1b is a potent inflammatory cytokine promptly expressed in activated myeloid immune cells. Among various transcription factors, PU.1 and CCAAT/enhancer-binding protein alpha (C/EBPa) play a key role in the lineage commitment of myeloid cells. To date, however, the exact mechanisms by which these lineage-determining transcription factors employ to regulate the expression of myeloid-specific genes remains elusive; thus, this study explores the role of PU.1 and C/EBPa in remodelling the chromatin conformation that allows ample production of IL-1b.

Methods: To examine the mechanism of these lineage-determining transcription factors, production of IL-1b and enhancer-promoter interactions were ...


Functional And Structural Mimicry Of A-Kinase Anchoring Proteins By Human Adenovirus E1a, Cason R. King Feb 2018

Functional And Structural Mimicry Of A-Kinase Anchoring Proteins By Human Adenovirus E1a, Cason R. King

Electronic Thesis and Dissertation Repository

As an obligate intracellular parasite, human adenovirus (HAdV) must utilize host factors for survival and replication. Early during infection, its multifunctional E1A protein interacts with an impressive range of cellular target proteins to exert control over the cellular environment. Through these virus-host interactions, E1A massively reprograms both viral and cellular transcription to activate the other HAdV genes, downregulate the host’s immune response, and induce the cell cycle. Consequently, E1A converts the infected cell into a compliant state more amenable for HAdV replication, resulting from its numerous protein-protein interactions. I sought to examine E1A’s interaction with cellular protein kinase ...


Amelioration Of Prenatal Alcohol Effects By Environmental Enrichment In A Mouse Model Of Fasd, Aniruddho Chokroborty-Hoque Aug 2017

Amelioration Of Prenatal Alcohol Effects By Environmental Enrichment In A Mouse Model Of Fasd, Aniruddho Chokroborty-Hoque

Electronic Thesis and Dissertation Repository

Maternal alcohol consumption during pregnancy results in a spectrum of behavioural and cognitive deficits collectively known as Fetal Alcohol Spectrum Disorders (FASD). Currently, little is know about if and how the external environment may modulate these deficits. I have used C57BL/6 mice to study this interaction between prenatal alcohol exposure and the postnatal environment. Alcohol exposure during synaptogenesis produces high levels of anxiety-like traits and decreased memory performance. Alcohol-exposed mice (and matched unexposed controls) were put in 'environmentally-enriched' conditions of voluntary exercise, physical activities and cognitive stimulation to ascertain the effects of a positive postnatal environment. The results show ...


Genetic Engineering Studies Of Escherichia Coli And Microalgae For Expression Of Hydrolytic Enzymes And Development Of High Throughput Screening Technique, Shreyas S. Yedahalli Jul 2017

Genetic Engineering Studies Of Escherichia Coli And Microalgae For Expression Of Hydrolytic Enzymes And Development Of High Throughput Screening Technique, Shreyas S. Yedahalli

Electronic Thesis and Dissertation Repository

The field of biochemical engineering has made substantial progress through major advances in genetic and metabolic engineering with applications in various sectors such as energy, food science, pharmaceuticals, etc. The hosts used for this work are constantly broadening. A host particularly important for energy applications are microalgae. The potential to enhance microalgae genetically for energy applications is not well explored and was therefore investigated in this thesis. Non-photosynthetic micro-organisms and photosynthetic microalgae offer a potential approach to enhance sustainable biochemical production. In this study expression vectors for Escherichia coli (E. coli) and Chlorella vulgaris (C. vulgaris) were constructed for the ...


Gmmyb176 Interactome And Regulation Of Isoflavonoid Biosynthesis In Soybean, Arun Kumaran Anguraj Vadivel Jun 2017

Gmmyb176 Interactome And Regulation Of Isoflavonoid Biosynthesis In Soybean, Arun Kumaran Anguraj Vadivel

Electronic Thesis and Dissertation Repository

MYB transcription factors are one of the largest transcription factor families characterized in plants. They are classified into four types: R1 MYB, R2R3 MYB, R3 MYB and R4 MYB. GmMYB176 is an R1MYB transcription factor that regulates Chalcone synthase (CHS8) gene expression and isoflavonoid biosynthesis in soybean. Silencing of GmMYB176 suppressed the expression of the GmCHS8 gene and reduced the accumulation of isoflavonoids in soybean hairy roots. However, overexpression of GmMYB176 does not alter either GmCHS8 gene expression or isoflavonoid levels suggesting that GmMYB176 alone is not sufficient for GmCHS8 gene regulation. I hypothesized that GmMYB176 acts cooperatively with another ...


Pore-Lining Residues And Intracellular Magnesium Concentration Influence Connexin50 Gap Junction Unitary Channel Conductance, Mary Grace M. Tejada Jun 2017

Pore-Lining Residues And Intracellular Magnesium Concentration Influence Connexin50 Gap Junction Unitary Channel Conductance, Mary Grace M. Tejada

Electronic Thesis and Dissertation Repository

Gap junction (GJ) channels mediate direct intercellular communication. Each GJ channel consists of two hemichannels and each hemichannel is a hexamer of connexins. GJs formed by different connexins display different unitary channel conductance (γj) and intracellular magnesium modulation. The underlying mechanisms are not fully clear. The present study investigates the effect of mutating putative pore-lining residues (G8, G46, and V53 individually or together) into glutamate in Cx50 on homotypic GJ channel properties. Expression of the triple and individual mutants in GJ-deficient N2A cells resulted in the formation of functional GJ channels similar to that of Cx50 GJs. However, the ...


Evolutionary Genetic Aspects Of Host Association In Generalist Ectoparasites, Benoit Talbot May 2017

Evolutionary Genetic Aspects Of Host Association In Generalist Ectoparasites, Benoit Talbot

Electronic Thesis and Dissertation Repository

Despite the use of the host for dispersal by most parasite species, the extremely loose relationship typical between highly mobile hosts and generalist ectoparasites may lead to very different gene flow patterns between the two, leading in turn to different spatial genetic structure, and potentially different demographic history. I examined how similar gene flow patterns are between Cimex adjunctus, a generalist ectoparasite of bats present throughout North America, and two of its key bat hosts. I first analyzed the continent-scale genetic structure and demographic history of C. adjunctus and compared it to that of two of its hosts, the little ...


The Cdk-Resistant Prb-E2f1 Complex Recruits Chromatin-Organizing Proteins To Repetitive Dna Sequences, Charles A. Ishak Apr 2017

The Cdk-Resistant Prb-E2f1 Complex Recruits Chromatin-Organizing Proteins To Repetitive Dna Sequences, Charles A. Ishak

Electronic Thesis and Dissertation Repository

This thesis investigates mechanistic links between genome integrity and the recruitment of chromatin organizing proteins to repetitive DNA sequences mediated by the retinoblastoma tumor suppressor protein (pRB). I demonstrate that a CDK-resistant interaction between the pRB C-terminus and the E2F1 coiled-coil marked box domain establishes a scaffold that facilitates recruitment of multiple chromatin-organizing proteins to repetitive sequences across the genome throughout the cell cycle. Specifically, pRB recruits the enhancer-of-zeste-homologue 2 (EZH2) histone methyltransferase to establish repressive facultative heterochromatin at repetitive sequences, and the Condensin II complex to ensure proper DNA replication and mitotic progression. To disrupt the CDK-resistant pRB-E2F1 interaction ...


Investigating E2f Independent Cell Cycle Control And Tumor Suppression By Prb, Michael J. Thwaites Apr 2017

Investigating E2f Independent Cell Cycle Control And Tumor Suppression By Prb, Michael J. Thwaites

Electronic Thesis and Dissertation Repository

Cellular division is primarily controlled at the G1 to S-phase transition of the cell cycle by the retinoblastoma tumor-suppressor protein (pRB). The ability of pRB to restrict S-phase entry is primarily attributed to the repression of E2F transcription factors required to upregulate cell cycle target genes necessary for cellular division. Interestingly, while pRB is disrupted in the vast majority of human cancers, mutations typically target upstream regulators of pRB leading to inactivation through hyperphosphorylation. The rarity of direct pRB mutations suggests that the regulation of the cell cycle by pRB may involve additional mechanisms outside of E2F repression, as this ...


Building Muscle: The Role Of Insulin-Like Growth Factor Binding Protein-6 And Insulin-Like Growth Factors In The Differentiation Of Placental Mesenchymal Stem Cells Into Skeletal Muscle, Doaa Aboalola Apr 2017

Building Muscle: The Role Of Insulin-Like Growth Factor Binding Protein-6 And Insulin-Like Growth Factors In The Differentiation Of Placental Mesenchymal Stem Cells Into Skeletal Muscle, Doaa Aboalola

Electronic Thesis and Dissertation Repository

Human placenta is a readily available source for isolation of adult mesenchymal stem cell (MSC), for potential use in regenerative therapies. MSC fate is influenced by the microenvironment in vivo, and insulin-like growth factors (IGFs) are critical components of the stem cell niche, as they regulate proliferation and differentiation into different lineages including bone, fat, and skeletal muscle. Insulin-like growth factor binding protein-6 (IGFBP-6), relative to other IGFBPs, has high affinity for IGF2 and is believed to be the main modulator of IGF-2 function. However, the role of IGFBP-6 in muscle development has not been clearly defined. In this study ...


The Effects Of Acetylenic Tricyclic Bis-(Cyano Enone) On Cell Migration, Eddie Chan Feb 2017

The Effects Of Acetylenic Tricyclic Bis-(Cyano Enone) On Cell Migration, Eddie Chan

Electronic Thesis and Dissertation Repository

Although cancer survival rates have significantly improved over the past few decades, the improvements are primarily due to early diagnosis and inhibiting cancer growth. Limited progress has been made in the treatment of cancer metastasis, which contributes to 90% of cancer related deaths, and therapeutic agents targeting the various aspects of metastasis are lacking. One potential approach is to utilize small pharmacological compounds to inhibit tumour cell motility, as a strategy against tumour cell migration, invasion, and metastasis. The acetylenic tricyclic bis-(cyano enone), TBE-31, has been shown to be a promising chemopreventative compound. However, its effects on cell migration ...


Cytosolic Acetyl-Coa Promotes Histone H3 Lysine 27 Acetylation In Arabidopsis, Chen Chen Feb 2017

Cytosolic Acetyl-Coa Promotes Histone H3 Lysine 27 Acetylation In Arabidopsis, Chen Chen

Electronic Thesis and Dissertation Repository

Acetyl-coenzyme A (acetyl-CoA) serves as a central metabolite in energy metabolism and biosynthesis. High level of acetyl-CoA can fuel the tricarboxylic acid (TCA) cycle to generate energy and store excess energy in fatty acids. Meanwhile, it also provides acetyl groups for protein acetylation, which normally occurs at the lysine or arginine residues. Acetylation regulates protein functions largely due to the change of total charges. Acetylation of histones, for example, can lead to loss of the interaction between histone and DNA, thus relaxing chromatin structure and potentially promoting gene expression. However, whether and how acetyl-CoA regulates plant chromatin remains unexplored. Here ...


The Association Between Oxidative Stress, Cellular Differentiation And Galectins In Human Promyelocytic Leukemia Cells (Hl-60), James R. Vinnai Dec 2016

The Association Between Oxidative Stress, Cellular Differentiation And Galectins In Human Promyelocytic Leukemia Cells (Hl-60), James R. Vinnai

Electronic Thesis and Dissertation Repository

Galectins are a group of β-galactoside-binding proteins involved in different cellular processes including stress responses and differentiation. The role and expression of galectins under oxidative stress and during neutrophilic differentiation was examined in HL-60 cells. Galectin gene (LGALS), and galectin protein expression were determined using RT-qPCR and immunoblotting, respectively. Neutrophilic differentiation was measured via a spectrofluorometric assay. DNA methylation and JNK signaling were investigated as galectin regulatory mechanisms. Menadione-induced oxidative stress, DMSO-induced differentiation, DNA hypomethylation and JNK signaling all promoted similar galectin expression profiles. Antioxidant N-acetylcysteine attenuated the menadione-induced galectin expression but only partially attenuated DMSO-induced galectin expression. Galectin inhibitory ...


Riboregulation Of Bacterial Transposons, Michael J. Ellis Dec 2016

Riboregulation Of Bacterial Transposons, Michael J. Ellis

Electronic Thesis and Dissertation Repository

Bacterial transposons typically exist in a mutually beneficial relationship with the host cell. Limited transposition can benefit the host while also ensuring the survival of the element. An important component of this relationship is that transposition must be tightly regulated. In this thesis I explore ways that the host and transposon each control transposition in E. coli and provide evidence that a transposon can also control host gene expression in S. enterica Typhimurium. Post-transcriptional regulation with small non-coding RNAs (sRNA) has emerged as a key way that bacteria respond to stress and regulate many cellular processes. The RNA-binding protein Hfq ...


Comprehensive Molecular Characterization Of Human Nodal, Scott D. Findlay Dec 2016

Comprehensive Molecular Characterization Of Human Nodal, Scott D. Findlay

Electronic Thesis and Dissertation Repository

Nodal and related ligands are highly conserved members of the TGF-beta superfamily with well-established and essential roles in the early embryonic development of vertebrates, and in cell fate decisions in human embryonic stem (hES) cells. Aberrant NODAL signaling also generally promotes pro-tumourigenic phenotypes and the progression of a wide array of human cancers. Despite being pursued as a potential therapeutic target, many aspects of NODAL’s molecular biology remain poorly understood. This thesis provides a comprehensive characterization of gene expression from the human NODAL locus at multiple levels. First, an intronic NODAL SNP known as rs2231947 was found to be ...


Freeze Tolerance Of Cyphoderris Monstrosa (Orthoptera: Prophalangopsidae), Jantina Toxopeus, Jacqueline Lebenzon, Alexander H. Mckinnon, Brent J. Sinclair Dec 2016

Freeze Tolerance Of Cyphoderris Monstrosa (Orthoptera: Prophalangopsidae), Jantina Toxopeus, Jacqueline Lebenzon, Alexander H. Mckinnon, Brent J. Sinclair

Biology Publications

The great grig, Cyphoderris monstrosa Uhler (Orthoptera: Prophalangopsidae), is a large (20-30 mm, >1 g), nocturnal ensiferan that in habits montane coniferous forests in northwestern North America. C. monstrosa overwinters as a late-instar nymph, but its cold tolerance strategy has not previously been reported. We collected nymphs from near Kamloops, British Columbia, in late spring to determine their cold tolerance strategy. C. monstrosa nymphs were active at low temperatures until they froze at -4.6 ± 0.3 °C. The nymphs survived internal ice formation (i.e. are freeze tolerant), had a lethal temperature between -9 and -12 °C, and could ...


Molecular Characterization Of Viruses Infecting Greenhouse Vegetables In Ontario, Bin Chen Oct 2016

Molecular Characterization Of Viruses Infecting Greenhouse Vegetables In Ontario, Bin Chen

Electronic Thesis and Dissertation Repository

Greenhouse vegetable production is a very important and successful agricultural sector in Ontario. However, newly emerging viral or virus-like diseases have become a major limiting factor in greenhouse vegetable production. To determine the identity of the viral pathogens in the three major greenhouse vegetables in Ontario, we conducted in-depth sequencing of small RNAs isolated from virally infected plants used next-generation sequencing technology. Subsequent bioinformatics analyses revealed six viral pathogens including Bell pepper endornavirus (BPEV), Parietaria mottle virus (PMoV), Cucumber green mottle mosaic virus (CGMMV), Tobacco streak virus (TSV), Pepper mild mottle virus (PMMoV), and Pepino mosaic virus (PepMV). The full-length ...


Development And Performance Evaluation Of An Antibody-Based Technology For Detection Of E. Coli O157 In Meat Samples And Its Potential Evolution Using Antibody Engineering, Yadira Tejeda Saldaña Sep 2016

Development And Performance Evaluation Of An Antibody-Based Technology For Detection Of E. Coli O157 In Meat Samples And Its Potential Evolution Using Antibody Engineering, Yadira Tejeda Saldaña

Electronic Thesis and Dissertation Repository

Escherichia coli O157 is a persistent pathogen linked to food and waterborne infectious outbreaks with severe health consequences such as hemorrhagic colitis and hemolyticuremic syndrome (HUS). Because it is considered one of the major pathogens that contributes to the global burden of foodborne disease, its early detection within the food chain is an important milestone towards reducing foodborne diseases and economic losses due to contaminated food. Herein, the development and validation of a lateral flow immunoassay (LFIA) point-of-care (POC) device is described. Application of the LFIA test kit was focused on detection of E. coli O157 in raw meat products ...


Characterization Of The Catalytic Ck2 Subunits With Substitutions At Residues Involved In Inhibitor Binding, Paul Desormeaux Sep 2016

Characterization Of The Catalytic Ck2 Subunits With Substitutions At Residues Involved In Inhibitor Binding, Paul Desormeaux

Electronic Thesis and Dissertation Repository

CK2 is a constitutively active, ubiquitously expressed and pleiotropic serine/threonine protein kinase that is implicated in many cellular functions including tumorigenesis. CK2 has two catalytic subunits, CK2a and CK2a’, that carry out its function in the cell. Previous studies have indicated that inhibitor-refractory mutants have been effective in recovering residual CK2 activity, in the presence of inhibitors, when compared to wild type CK2. Based on these observations, inhibitor-refractory mutants were created for both CK2a and CK2a’ and tested with various concentrations with two CK2-specific inhibitors, CX-4945 and inhibitor VIII. The CK2a triple mutant (V66A/I174A/H160D) was tested in ...


Multi-Gene Resistance To Neonicotinoids In The Colorado Potato Beetle, Leptinotarsa Decemlineata, Emine Kaplanoglu Aug 2016

Multi-Gene Resistance To Neonicotinoids In The Colorado Potato Beetle, Leptinotarsa Decemlineata, Emine Kaplanoglu

Electronic Thesis and Dissertation Repository

The Colorado potato beetle, Leptinotarsa decemlineata, is a significant pest of potato, and its impact on agriculture is measured on a global scale. The beetle is mainly controlled by neonicotinoid insecticides, however, resistance development is a growing concern. Resistance to neonicotinoids is thought to involve elevated activity of detoxifying enzymes and xenobiotic transporters that break-down and excrete insecticide molecules. Here, using mRNA sequencing, I identified multiple detoxifying enzyme and xenobiotic transporter genes transcriptionally up-regulated in a neonicotinoid resistant strain of beetles. I then used RNA interference to knock down the transcript levels of the ten most promising genes in resistant ...


Iron Acquisition Strategies Employed By Staphylococcus Lugdunensis, Jeremy R. Brozyna Aug 2016

Iron Acquisition Strategies Employed By Staphylococcus Lugdunensis, Jeremy R. Brozyna

Electronic Thesis and Dissertation Repository

Iron is crucial for many cellular processes including DNA synthesis and respiration. The majority of iron in mammals is in heme within hemoproteins, inside cells, or transported through circulation by the glycoprotein transferrin, which constitutes the greatest iron source in serum. Limiting iron availability is an important facet of nutritional immunity to help prevent infection.

Staphylococcus lugdunensis is a human skin commensal and opportunistic pathogen capable of causing a variety of infections, including particularly aggressive endocarditis. It is an emerging pathogen with elevated virulence compared to other species of coagulase-negative staphylococci. The versatility of S. lugdunensis to infect multiple niches ...


Insights Into Chibby's Structural Elements And Their Interplay In Wnt Signaling Protein-Protein Interactions, Ryan C Killoran Aug 2016

Insights Into Chibby's Structural Elements And Their Interplay In Wnt Signaling Protein-Protein Interactions, Ryan C Killoran

Electronic Thesis and Dissertation Repository

The Wnt/b-catenin signaling pathway is critical to embryonic development and adult tissue homeostasis. Mutations to Wnt signaling components can cause dysregulation of the pathway, leading to various human diseases such as cancer. The partially disordered protein Chibby (Cby) is a conserved nuclear protein that acts as an antagonist in the Wnt/b-catenin signaling pathway. Cby’s antagonism is accomplished via two mechanisms. First, by competing with the Tcf/Lef family of transcription factors, Cby abrogates the b-catenin-mediated transcription of Wnt signaling genes. Moreover, upon phosphorylation on serine 20 by the kinase Akt, Cby forms a complex with the protein ...


Cal And Magi Pdz Protein Regulation Of Crfr1 And 5-Ht2ar Trafficking And Signaling, Maha Mahmoud Hammad Aug 2016

Cal And Magi Pdz Protein Regulation Of Crfr1 And 5-Ht2ar Trafficking And Signaling, Maha Mahmoud Hammad

Electronic Thesis and Dissertation Repository

PDZ (PSD95/Disc Large/Zona Occludens) domain-containing proteins are scaffolding proteins that play important roles in regulating the activity of G protein-coupled receptors. Corticotropin Releasing Factor Receptor 1 (CRFR1) and Serotonin 2A Receptor (5-HT2AR) are two GPCRs that are commonly associated with mental disorders. Both receptors also contain a class I PDZ-binding motif at the carboxyl terminal tail. In the first chapter, we investigate the effects of CAL (CFTR-associated ligand) on regulating the trafficking and signaling of CRFR1. We demonstrate a role for CAL in inhibiting CRFR1 endocytosis, cell surface expression, and CRF-mediated ERK1/2 signaling via the ...


Regulation Of Phosphatase And Tensin Homolog Expression And Activity By Transforming Growth-Factor Beta In The Trabecular Meshwork Cells: Implications For Primary Open Angle Glaucoma, Nikoleta Tellios Jun 2016

Regulation Of Phosphatase And Tensin Homolog Expression And Activity By Transforming Growth-Factor Beta In The Trabecular Meshwork Cells: Implications For Primary Open Angle Glaucoma, Nikoleta Tellios

Electronic Thesis and Dissertation Repository

Glaucoma is a multifactorial condition caused, in part, by fibrosis of the sieve-like trabecular meshwork (TM) tissue, which impedes drainage of aqueous humor (AH), leading to increased intraocular pressure and associated optic nerve damage and blindness. Fibrosis of the TM is mainly caused by the increased levels of active transforming growth factor-β 2 (TGFβ2) in the AH of glaucoma patients.

Previous reports have shown that TGFβ decreases the expression of Phosphatase and Tensin Homolog (PTEN) gene and that PTEN is a major regulator of ECM deposition. In this study we investigate the regulation of PTEN protein expression and activity by ...


Characterization Of Numb As A Regulator Of Anaplastic Lymphoma Kinase, Ran Wei Jun 2016

Characterization Of Numb As A Regulator Of Anaplastic Lymphoma Kinase, Ran Wei

Electronic Thesis and Dissertation Repository

Cellular events rely on protein-protein interactions that are often mediated by modular domains which recognize particular sequence motifs in binding partners. The NUMB protein is the first described cell fate determinant and multifaceted adaptor that is involved in a wide variety of cellular events. NUMB mainly mediates protein interactions via its modular PTB domain. Here we present a systematic investigation of the NUMB-PTB interactome by employing an integrative strategy combining both protein and peptide arrays. We profiled NUMB-PTB binding specificity and interacting proteins genome-wide. The receptor tyrosine kinases (RTKs) are found highly enriched in the interactome, raising the possibility that ...