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Articles 691 - 720 of 13228
Full-Text Articles in Biochemistry, Biophysics, and Structural Biology
Discovering Localization Of Fun19 Orf In Yeast, Megan Percy, Galayna Baur, Katie Shannon
Discovering Localization Of Fun19 Orf In Yeast, Megan Percy, Galayna Baur, Katie Shannon
Miners Solving for Tomorrow Research Conference
No abstract provided.
Carrier Analysis Of Alc Lipid Nanoparticles With Lung Cancer Drug, Noah Sparks, Lei Xu, Hu Yang
Carrier Analysis Of Alc Lipid Nanoparticles With Lung Cancer Drug, Noah Sparks, Lei Xu, Hu Yang
Miners Solving for Tomorrow Research Conference
No abstract provided.
Characterization Of An Iqg1 Phosphorylation Mutant, Lindsay Scheider, Alexis Ham, Katie Shannon
Characterization Of An Iqg1 Phosphorylation Mutant, Lindsay Scheider, Alexis Ham, Katie Shannon
Miners Solving for Tomorrow Research Conference
No abstract provided.
The Effects Of Preventing Dephosphorylation Of Iqg1 On Cytokinesis, Jenna L. Mueller, Katie Shannon
The Effects Of Preventing Dephosphorylation Of Iqg1 On Cytokinesis, Jenna L. Mueller, Katie Shannon
Miners Solving for Tomorrow Research Conference
No abstract provided.
Metabolic Transitions In Embryos Of Artemia Franciscana: Regulation And Consequences For Oxidative Stress, Daniel Anthony Arabie
Metabolic Transitions In Embryos Of Artemia Franciscana: Regulation And Consequences For Oxidative Stress, Daniel Anthony Arabie
LSU Doctoral Dissertations
Embryos of Artemia franciscana survive harsh conditions in diapause and anoxia-induced quiescence for years by undergoing deep metabolic transitions. I investigated the relationship between phosphorylation of pyruvate dehydrogenase (PDH) and carbon flux to the tricarboxylic acid (TCA) cycle during metabolic depression. The difference in catalytic activity of the PDH complex (PDC) in maximally phosphorylated and dephosphorylated samples was 16.5-fold. Western blot analysis confirmed the changes in phosphorylation of PDH. Analysis of PDH expression in diapause and post-diapause embryos via phospho-PDH showed no significant differences. Investigation of post-diapause embryos under anoxia showed that phosphorylation of PDH decreased and activated the enzyme. …
Toward Ar Visualization Of The Fluid-Mosaic Model Of The Cell Membrane, Yoonwoo Lee, Allison Ost, Junghyuk Lee, Krisztina Z. Bencze
Toward Ar Visualization Of The Fluid-Mosaic Model Of The Cell Membrane, Yoonwoo Lee, Allison Ost, Junghyuk Lee, Krisztina Z. Bencze
SACAD: Scholarly Activities
Background: During the first semester of biochemistry experience, students focus on learning the structure and function of biomolecules: carbohydrates, lipids, proteins, and nucleic acids. Visualizing these structures and understanding interactions between molecules helps students better understand biological function. A variety 3D visualization tools are available, ex. PyMol, Chimera, Avogadro, Blender. Within the past decade, Augmented Reality (AR) and Virtual Reality (VR) applications gained more popularity. VR with its immersive visual experience is more sought-after, but the higher cost and the need for headset creates limitations in the classroom. AR visualizations are cheaper and more accessible, several publications report successful implementation …
Host P53 Expression During C. Parvum Infection…Does The Virus Play A Role?, Jasdeep Kaur Dhanoa
Host P53 Expression During C. Parvum Infection…Does The Virus Play A Role?, Jasdeep Kaur Dhanoa
Biochemistry and Molecular Biology
C. parvum infection induces significant host cellular stress responses, particularly through the modulation of p53 expression underscoring its potential involvement in gastrointestinal malignancies. Understanding these mechanisms is crucial for developing targeted therapeutic interventions. This study investigated the effects of C. parvum infection on host p53 dynamics in HCT-8 cells and assessed the impact of antiviral agents Lamivudine and Amantadine on the virus CSpV1 present within the parasite C. parvum. Further, the study focuses on whether the p53 effect changes with the presence or absence of CSpV1. The p53 assay results showed a constant increase in p53 activity after infection of …
Resurrecting The Past: Engineering Ancestral Enzymes For Modern Bacterial Applications, Gregory M. Gladkowski Iii, Masa Watanabe
Resurrecting The Past: Engineering Ancestral Enzymes For Modern Bacterial Applications, Gregory M. Gladkowski Iii, Masa Watanabe
SACAD: Scholarly Activities
Ancestral Sequence Reconstruction (ASR) is a computational technique that infers and resurrects ancient protein sequences to explore molecular evolution and enable protein engineering. By integrating phylogenetics and statistical modeling, ASR produces stable, mutation-tolerant enzymes ideal for directed evolution. This poster presents a workflow for reconstructing enzymes from pathogenic bacteria and highlights ASR’s value in uncovering novel functions and advancing applications in drug discovery and synthetic biology.
Proteomic-Based Strategies To Determine Aberrant Signaling In Cancer, Natasha Chipman Mariano
Proteomic-Based Strategies To Determine Aberrant Signaling In Cancer, Natasha Chipman Mariano
Dartmouth College Ph.D Dissertations
Proteomics and phosphoproteomics have emerged as powerful tools to elucidate the intricate molecular underpinnings that drive cancer development by quantifying changes in protein and post-translational modification abundances. Throughout my thesis work, I have advanced these techniques to map cancer signaling networks on a global scale. Among breast cancer subtypes, triple-negative (TNBC) remains the most challenging to treat, with poorer clinical outcomes attributed to tumor heterogeneity and yet unidentified, oncogenic driver proteins for therapeutic targeting. To identify potential targeted treatment strategies, we employed mass spectrometry-based quantitative proteomics to analyze 55 formalin-fixed paraffin- embedded TNBC tumor specimens. Unsupervised hierarchical clustering of relative …
Kinetic Control And Trapping In The Supramolecular Polymerization Of M-Terphenyl Bis-Urea Macrocycles, Sophya V. Garashchuk, Gamage Isuri P. Wijesekera, Isabella G. Rushton, Vaibhavi A. Samant, Fahidat A. Gbadamosi, Dr. Md Faizul Islam, Sophya V. Garashchuk, Prof. Dr. Linda S. Shimizu
Kinetic Control And Trapping In The Supramolecular Polymerization Of M-Terphenyl Bis-Urea Macrocycles, Sophya V. Garashchuk, Gamage Isuri P. Wijesekera, Isabella G. Rushton, Vaibhavi A. Samant, Fahidat A. Gbadamosi, Dr. Md Faizul Islam, Sophya V. Garashchuk, Prof. Dr. Linda S. Shimizu
Faculty Publications
Herein, we examine pathway complexity in the supramolecular polymerization of a novel m-terphenyl bis-urea macrocycle. Designed to induce kinetically metastable states, the macrocycle‘s concentration-dependent aggregation was studied via 1H NMR and IR spectroscopy in THF and CHCl₃. Temperature-dependent UV-Vis spectroscopy in water/THF revealed a cooperative nucleation-growth mechanism, indicated by a shift in λmax to longer wavelengths upon cooling. Morphological studies using DLS, AFM, and SEM demonstrated fibrous aggregate formation. Thermal hysteresis observed in assembly-disassembly cycles indicated kinetically trapped species, with cooling governed by kinetic control and heating by thermodynamic processes. Deviations in ΔH values during cooling, compared to van′t …
How The Biotic And Abiotic Factors In The Belle Forest Cave And Arboretum Soil Dictates Tree Species Prevalence, Amya A. Bingham
How The Biotic And Abiotic Factors In The Belle Forest Cave And Arboretum Soil Dictates Tree Species Prevalence, Amya A. Bingham
SPARK Symposium Presentations
A plethora of factors in the soil impact a plant’s health, including the presence of different biotic and abiotic factors. These include things like temperature, elevation, pH, microbial respiration and the presence of water, clay, loam, silt, sand, nitrogen, potassium, and phosphorus. Different soils will have varying amounts of these, which may dictate what is able to grow in them, and therefore also the surrounding area. This research project explores how the aforementioned biotic and abiotic factors affect the soil at the Belle Forest Cave and Arboretum. Three samples will be taken from four spots along a transect at this …
Dental Disparities: An Analysis Of Dental Caries Risk Factors Promoting Disparities Between Rural And Urban Communities In Nebraska, Nick Lounsbery
Dental Disparities: An Analysis Of Dental Caries Risk Factors Promoting Disparities Between Rural And Urban Communities In Nebraska, Nick Lounsbery
Honors Program: Senior Projects (Public)
The prevalence of dental caries in the United States remains a public health concern, as it is one of the most common chronic conditions across people of all ages. Research shows that preventative measures including brushing, fluoridated water, and regular checkups are effective strategies to mitigate tooth decay. However, there appears to be a divide between rural and urban populations, as the presence of dental cavities is significantly greater in remote areas in the State of Nebraska. Research methods used in this analysis included analyzing accredited academic literature to illustrate how cavities form from a biochemical perspective. Research methods also …
Investigation Of The Effects Of The Peptidylarginine Deiminase Inhibitor Cl-Amidine On Apoptosis And Gene Expression In Ovarian Cancer, Victoria Walden
Investigation Of The Effects Of The Peptidylarginine Deiminase Inhibitor Cl-Amidine On Apoptosis And Gene Expression In Ovarian Cancer, Victoria Walden
Longwood Senior Thesis Proposal
Peptidylarginine deiminases (PADs) are a family of enzymatic proteins responsible for the conversion of arginine and methylarginine residues to citrulline. This conversion is important for several key cellular processes including transcriptional gene regulation. Recently, a link has been established between overexpression of a particular PAD, PAD4, and the accelerated progression of both autoimmune diseases and cancers. Ovarian cancer exhibits heightened levels of PAD4 in affected cells. High levels of PAD4 are associated with the formation of neutrophil extracellular traps (NETs) that promote cancer metastasis, and downregulation of the p53 apoptotic pathway. Thus, it is important to explore inhibitors of PAD4. …
College Of Natural Sciences Newsletter, Spring 2025, College Of Natural Sciences
College Of Natural Sciences Newsletter, Spring 2025, College Of Natural Sciences
College of Natural Sciences Newsletters and Reports
Page 1 Dean's Message from Dr. Sen Subramanian
Page 2 Student Spotlights
Page 3 Kaushik honored, Three-Minute Thesis, & Ice Cores revealed
Page 4 Alumni Spotlight
Page 5 Day of Scholars
Page 6 Cyanide research, Record Research Expenditures, Adhikari awarded Miller Research Award
Page 8 Hanson Receives NSF Grant
Page 9 Snow Lab Research Team
Page 10 Faculty Awards
Page 11 Drone Day
Page 13 Khalaf Awarded Presidential Award
Development Of Flexible Lactate-Specific Molecularly Imprinted Polymers Based On Laser-Induced Graphene Electrochemical Biosensors For Disease Diagnosis, Christopher Animashaun
Development Of Flexible Lactate-Specific Molecularly Imprinted Polymers Based On Laser-Induced Graphene Electrochemical Biosensors For Disease Diagnosis, Christopher Animashaun
Biomedical Engineering Theses & Dissertations
Lactate is a critical biomarker linked to conditions such as sepsis, ischemia, cancer, and heart failure. Current lactate detection methods remain invasive, costly, and unsuitable for real-time, continuous monitoring. This study presents the development of a flexible, non-enzymatic electrochemical biosensor based on laser-induced graphene (LIG) electrodes modified with gold nanoparticles (AuNPs) and molecularly imprinted polymers (MIPs) for highly selective and sensitive lactate measurement. The integration of AuNPs enhanced surface conductivity and provided nanoscale heterogeneity, facilitating superior signal amplification. The optimized LIG/AuNP/MIP sensor achieved an extensive dynamic detection range from 0.1 μM to 1000 μM, with an outstanding detection limit of …
Steroid Receptors And Coregulators: Dissemination Of Sex Differences And Emerging Technologies, Sally Pauss, Evelyn A. Bates, Genesee J. Martinez, Zane T. Bates, Zachary A. Kipp, Cassandra D. Gipson, Terry D. Hinds Jr.
Steroid Receptors And Coregulators: Dissemination Of Sex Differences And Emerging Technologies, Sally Pauss, Evelyn A. Bates, Genesee J. Martinez, Zane T. Bates, Zachary A. Kipp, Cassandra D. Gipson, Terry D. Hinds Jr.
Markey Cancer Center Faculty Publications
Steroid receptors are ligand-induced transcription factors that have broad functions among all living animal species, ranging from control of sex differences, body weight, stress responses, and many others. Their binding to coregulator proteins is regulated by corepressors and coactivators that interchange upon stimulation with a ligand. Coregulator proteins are an imperative and understudied aspect of steroid receptor signaling. Here, we discuss steroid receptor basics from protein domain structures that allow them to interact with coregulators and other proteins, their essential functions as transcription factors, and other elemental protein–protein interactions. We deliberate about the mechanisms that coregulators control in steroid receptor …
Ccr7 Regulated Mechanisms That Limit The Adaptive Immune Response, Jaisel Amilcar Cervantes
Ccr7 Regulated Mechanisms That Limit The Adaptive Immune Response, Jaisel Amilcar Cervantes
Open Access Theses & Dissertations
C-C chemokine receptor 7 (CCR7) is critical in guiding T cell migration within the thymus and peripheral lymphoid tissues, shaping the adaptive immune response by promoting central tolerance and regulating immune homeostasis. Although its role in lymphocyte trafficking is well established, the molecular mechanisms by which CCR7 influences thymocyte development and T cell receptor (TCR) repertoire formation remain less understood. This study examines how CCR7 deficiency impacts thymic selection, TCR diversity, and the signaling events that shape repertoire restriction. Using a homozygously deleted CCR7 murine model, we found that the absence of CCR7 results in a less restricted TCR repertoire …
Expanding The Lexa Bacterial Two-Hybrid System For Human Protein-Protein Interaction Screening: Application To Tumor Suppressor Par-4, Rebecca M. Richardson
Expanding The Lexa Bacterial Two-Hybrid System For Human Protein-Protein Interaction Screening: Application To Tumor Suppressor Par-4, Rebecca M. Richardson
Chemistry & Biochemistry Theses & Dissertations
Protein-protein interactions (PPI) are fundamental to cellular function, influencing processes such as signaling, structural organization, and disease progression. Disruptions in PPIs are implicated in cancer and neurodegenerative diseases, highlighting their importance as therapeutic targets. However, traditional methods for studying human PPIs, such as yeast two-hybrid and co-immunoprecipitation mass spectrometry, are costly and technically demanding. This dissertation explores the LexA-based bacterial two-hybrid (LexA-B2H) system as a cost effective and accessible alternative for investigating human PPIs.
This study focuses on the interaction between glucose-regulated protein 78 (GRP78) and cleaved prostate apoptosis response-4 (cl-Par-4), a tumor suppressor protein involved in apoptosis and neurodegenerative …
Next-Generation Biomedical Implants And Stimuli Responsive Soft Optical Arrays Via Surface Functionalized Elastomeric Materials, John M. Kapitan
Next-Generation Biomedical Implants And Stimuli Responsive Soft Optical Arrays Via Surface Functionalized Elastomeric Materials, John M. Kapitan
Dissertations and Doctoral Documents, University of Nebraska-Lincoln, 2023–
The demands of emerging technologies, such as soft robotics, stretchable electronics, and next generation biomedical implants, has led to the development of diverse polymeric and hybrid organic/inorganic materials specifically tuned to meet these challenges. These materials typically have low Young’s moduli and are inert with high chemical stability. However, this has led to materials that are static in nature, lacking any meaningful way of responding to changes in their environment and adapting to these changes. This has driven a shift towards the design, manufacturing, and characterization of various stimuli responsive surfaces, relying on precise control of surface chemical coatings and …
Low Dissolved Oxygen Operation Enhances Biological Phosphorus Removal In Wastewater Treatment, Haley Morgan
Low Dissolved Oxygen Operation Enhances Biological Phosphorus Removal In Wastewater Treatment, Haley Morgan
Civil & Environmental Engineering Theses & Dissertations
Biological phosphorus (bio-P) removal occurs when bacteria are exposed to anaerobic/aerobic conditions that stimulate polyphosphate-accumulating organisms (PAOs) to uptake phosphorus. In most treatment plants, dissolved oxygen (DO) concentrations in the aeration tanks are commonly at or above 2.0 mg O2/L, which is often referred to as the most optimal aeration condition for bio-P. If bio-P can happen efficiently at lower DO (< 0.3 mg O2/L), then the energy demand of aeration can be decreased appreciably. This research was conducted in a biological nutrient removal (BNR) pilot plant to assess the performance of bio-P at progressively lower DO operation. This …
Crispr-Induced Mutagenesis Of Arabidopsis Thaliana Gene Apetala3, Hazel Frans, Tara Phelps-Durr
Crispr-Induced Mutagenesis Of Arabidopsis Thaliana Gene Apetala3, Hazel Frans, Tara Phelps-Durr
SACAD: Scholarly Activities
This project aims to create CRISPR-CAS9 mutations in the APETELA3 (AP3) gene of the model plant Arabidopsis thaliana. AP3 is a class B gene critical to the petal and stamen development of Arabidopsis flowers. AP3 is defined in a MADS domain, which binds directly to DNA and may be responsible for the expression of the CaRG-box genes. AP3 works in conjunction with PISTILLATA (PI), AGAMOUS (AG), APETALA1 (AP1), and SEPALLATA (SEP) genes to specify the development in the second and third whorls of the flower. While several alleles of AP3 already exist, these alleles are strong alleles that knockout gene …
Painting Rich Six-Dimensional Pictures Using Polarized Fluorescence Microscopy, Matthew D. Lew
Painting Rich Six-Dimensional Pictures Using Polarized Fluorescence Microscopy, Matthew D. Lew
Electrical & Systems Engineering Publications and Presentations
No abstract provided.
Dnajb6: A Potent Dnajb Chaperone In Regulating Tau Proteostasis, Abigail R. Esquivel
Dnajb6: A Potent Dnajb Chaperone In Regulating Tau Proteostasis, Abigail R. Esquivel
USF Tampa Graduate Theses and Dissertations
Neurodegenerative diseases often feature the pathological buildup of misfolded proteins, and tau is a principal culprit in multiple tauopathies. One chaperone of emerging interest is DnaJB6b, a member of the Hsp40/DnaJ family, which exhibits potent anti-aggregation activity against several disease-related proteins. Recent investigations highlight its unique capacity to recognize and neutralize aggregation-prone forms of tau. DnaJB6b appears potent against multiple variants of tau and may be acting against tau, in part, by directing misfolded tau toward proteasomal clearance. The first lines of evidence come from systematic chaperone screens, where DnaJB6b repeatedly emerged as a strong suppressor of tau seeding. Further …
Functional Connectivity Of Red Chlorophylls In Cyanobacterial Photosystem I Revealed By Fluence-Dependent Transient Absorption, Sara Sohail, S. Sohoni, P.-C. Ting, L. R. Fantz, S. M. Abdulhadi, C. Macgregor-Chatwin, A. Hitchcock, C. N. Hunter, G. S. Engel, S. C. Massey
Functional Connectivity Of Red Chlorophylls In Cyanobacterial Photosystem I Revealed By Fluence-Dependent Transient Absorption, Sara Sohail, S. Sohoni, P.-C. Ting, L. R. Fantz, S. M. Abdulhadi, C. Macgregor-Chatwin, A. Hitchcock, C. N. Hunter, G. S. Engel, S. C. Massey
Chemistry & Biochemistry Faculty Works
External stressors modulate the oligomerization state of photosystem I (PSI) in cyanobacteria. The number of red chlorophylls (Chls), pigments lower in energy than the P₇₀₀ reaction center, depends on the oligomerization state of PSI. Here, we use ultrafast transient absorption spectroscopy to interrogate the effective connectivity of the red Chls in excitonic energy pathways in trimeric PSI in native thylakoid membranes of the model cyanobacterium Synechocystis sp. PCC 6803, including emergent dynamics, as red Chls increase in number and proximity. Fluence-dependent dynamics indicate singlet–singlet annihilation within energetically connected red Chl sites in the PSI antenna but not within bulk Chl …
Induced Mutagenesis In West Nile Virus Non-Structural Protein 3 With A Discussion Of The Mutation's Effects On Viral Properties, Caden Connealy
Induced Mutagenesis In West Nile Virus Non-Structural Protein 3 With A Discussion Of The Mutation's Effects On Viral Properties, Caden Connealy
Honors Program: Senior Projects (Public)
West Nile Virus (WNV), a member of the Flaviviridae family and introduced to the Western hemisphere in 1999, presents a unique and emerging threat to human health. Infection in humans is often mild but can occasionally result in severe neurological impairment and even death. West Nile Virus non-structural protein 3 (NS3) plays an important role in the process of viral genome amplification. More specifically, the C-terminal domain of the protein folds into a helicase enzyme, which is responsible for the “unwinding” of double-stranded RNA intermediates and RNA secondary structure on the WNV genome. This is a vitally important step in …
College Of Natural Sciences 2024 Year-End Publication, College Of Natural Sciences
College Of Natural Sciences 2024 Year-End Publication, College Of Natural Sciences
College of Natural Sciences Newsletters and Reports
Page 2 Dean's Message
Page 3 Department Highlights
Page 4 One Day for State
Page 5 New Students in Wecota
Page 6-8 Faculty Excellence
Page 9 SDSU Physics Students Recognized
Page 9 Prairie Doc Watch Party
Page 10-11 Student Excellence
Page 11 Connections Abroad
Page 12-13 CNS’s Research Centers
Page 14 Connections Abroad
Page 14 Dean Wolf-Hall Retired
Page 15 Outreach Program
Page 15 Events and Traditions
Page 16 Student Spotlight
Page 17 Alumni Spotlight
Page 18-19 SDSU Alum at Paris Paralympics
Page 20 Work Anniversaries & Programs
Domain Communication In Bifunctional Proline Utilization A From Sinorhizobium Meliloti, Emma Bitterman
Domain Communication In Bifunctional Proline Utilization A From Sinorhizobium Meliloti, Emma Bitterman
Honors Program: Senior Projects (Public)
The reduction potential of flavin bound to Sinorhizobium meliloti proline utilization A (SmPutA) is beneficial in providing vital information on enzyme activity and the active site environment. Flavin is crucial in biological metabolism such as aerobic respiration and other important processes like oxygen activation that are catalyzed by flavin-dependent enzymes. (4). In this study, we seek to determine whether the redox potential of SmPutA-bound flavin can be used to characterize potential long-distance communication and analyze the possibilities of inactivation reversibility. SmPutA is a large bifunctional enzyme that catalyzes the overall oxidation of proline to glutamate via two catalytic domains (1). …
Development, Optimization, And Validation Of A High-Sensitivity Capillary Zone Electrophoresis System For Bioanalytical Applications, Aaron I. Mena
Development, Optimization, And Validation Of A High-Sensitivity Capillary Zone Electrophoresis System For Bioanalytical Applications, Aaron I. Mena
Electronic Theses and Dissertations
Capillary zone electrophoresis (CZE) is a powerful analytical technique widely used for biomolecular separation due to its high resolution, efficiency, and sensitivity. This report presents the development and validation of a novel CZE system designed to improve modularity, reproducibility, and operational efficiency. The system integrates a laser-induced fluorescence (LIF) detection method with a 488 nm laser, enhanced fluid control through a negative pressure system, and a user-friendly GUI for automated operation and data acquisition. Performance verification included pressure stability tests, fluorescence accuracy assessments, and electrophoretic reproducibility studies. Comparative analysis with a previous CZE iteration confirmed improved baseline stability, peak resolution, …
Synthetic Protein Mimetic Based Therapies For Neurodegeneration, Nicholas H. Stillman
Synthetic Protein Mimetic Based Therapies For Neurodegeneration, Nicholas H. Stillman
Electronic Theses and Dissertations
Protein-protein interactions (PPIs) are crucial for the regulation of a majority of, if not every fundamental cellular process. Despite their role in regular biological processes, dysregulated and/or aberrant protein-protein interactions (aPPIs) are often related to the onset of disease including cancer, viral infection, and amyloid diseases. aPPIs have historically been deemed ‘undruggable’ due to their large surface area and lack of a binding cavity; however, today, more than 40 disease-related aPPIs have been targeted with small molecules and several of those have reached clinical trials.
A class of synthetic protein mimetics called oligopyridylamides (OPs) has been shown to inhibit disease-related …
The Guanine Nucleotide Exchange Factor Ric-8a Regulates The Sensitivity Of Constitutively Active Gαq To The Inhibitor Ym-254890, Morgan Dwyer, Jiansong Luo, Tyson Todd, Kendall Blumer, Gregory Tall, Philip Wedegaertner
The Guanine Nucleotide Exchange Factor Ric-8a Regulates The Sensitivity Of Constitutively Active Gαq To The Inhibitor Ym-254890, Morgan Dwyer, Jiansong Luo, Tyson Todd, Kendall Blumer, Gregory Tall, Philip Wedegaertner
Department of Biochemistry and Molecular Biology Faculty Papers
Heterotrimeric G proteins are stimulated under normal circumstances by G protein-coupled receptors to promote downstream intracellular signaling. Mutations can occur in αq at glutamine 209 (Q209) that cause constitutive, G protein-coupled receptor independent signaling due to disruption of GTPase activity. Specifically, Q209L/P mutations are oncogenic drivers of uveal melanoma. YM-254890 (YM) has been shown to selectively inhibit both WT and constitutively active (CA) αqQ209L/P by preventing the release of GDP and exchange for GTP, thereby halting downstream signaling. Because αqQL/P are thought to be primarily GTP-bound and GTPase deficient, the current mechanistic understanding of YM inhibition needs further investigation to …