Medicine and Health Sciences Commons^™

September / October 2021, Randy Curry, Cindy Brooks

RURAL ROCKS

Rural Rocks, the Rural Health Network newsletter by the SWOSU College of Pharmacy.

Bioactive Nanotherapeutic Trends To Combat Triple Negative Breast Cancer, Pallabita Chowdhury, Upasana Ghosh, Kamalika Samanta, Meena Jaggi, Subhash C. Chauhan, Murali M. Yallapu

School of Medicine Publications and Presentations

The management of aggressive breast cancer, particularly, triple negative breast cancer (TNBC) remains a formidable challenge, despite treatment advancement. Although newer therapies such as atezolizumab, olaparib, and sacituzumab can tackle the breast cancer prognosis and/or progression, but achieved limited survival benefit(s). The current research efforts are aimed to develop and implement strategies for improved bioavailability, targetability, reduce systemic toxicity, and enhance therapeutic outcome of FDA-approved treatment regimen. This review presents various nanoparticle technology mediated delivery of chemotherapeutic agent(s) for breast cancer treatment. This article also documents novel strategies to employ cellular and cell membrane cloaked (biomimetic) nanoparticles for effective clinical …

Preliminary Findings Of A Study On The Practice Of Self-Medication Of Antibiotics Among The Practicing Nurses Of A Tertiary Care Hospital, Akbar Shoukat Ali, Rahim Jandani, Arwa A. Al-Qahtani, Abdulkarem A S. Alenzi

Department of Medicine

Objectives: Antibiotic resistance is indeed a global concern. It is of significant concern especially in the low-middle income countries because of the ease of accessibility, affordability, and absence of regulations pertaining to the dispensing of non-prescription antibiotics. This study aims to estimate the frequency and factors associated with the self-medication of antibiotics found among the practicing nurses.
Methods: We conducted a descriptive cross-sectional study at a tertiary care hospital in Karachi, Pakistan from July 2016 to August 2016.
Results: Of the 48 recruited nurses, 60.4% (29/48) were practicing self-medication of antibiotics. There were slightly more male nurses (17/29) than their …

The Costs Of Developing Treatments For Alzheimer’S Disease: A Retrospective Exploration, Jeffrey L. Cummings, Dana P. Goldman, Nicholas R. Simmons-Stern, Eric Ponton

School of Medicine Faculty Publications

Introduction: With the exception of the recent accelerated approval of aducanumab, in over 26 years of research and development (R&D) investment in Alzheimer's disease (AD), only five novel drugs—all for symptomatic treatment only—have reached FDA approval. Here, we estimate the costs of AD drug development during this period in the private sector. Methods: To estimate private R&D funding, we collected information on AD clinical trials (n = 1099; phases 1–4) conducted between January 1, 1995 and June 21, 2021 from various databases. Costs were derived using previously published methodologies and adjusted for inflation. Results: Since 1995, cumulative private expenditures on …

Atomistic Simulations And In Silico Mutational Profiling Of Protein Stability And Binding In The Sars-Cov-2 Spike Protein Complexes With Nanobodies: Molecular Determinants Of Mutational Escape Mechanisms, Gennady M. Verkhivker, Steve Agajanian, Deniz Yasar Oztas, Grace Gupta

Mathematics, Physics, and Computer Science Faculty Articles and Research

Structure-functional studies have recently revealed a spectrum of diverse high-affinity nanobodies with efficient neutralizing capacity against SARS-CoV-2 virus and resilience against mutational escape. In this study, we combine atomistic simulations with the ensemble-based mutational profiling of binding for the SARS-CoV-2 S-RBD complexes with a wide range of nanobodies to identify dynamic and binding affinity fingerprints and characterize the energetic determinants of nanobody-escaping mutations. Using an in silico mutational profiling approach for probing the protein stability and binding, we examine dynamics and energetics of the SARS-CoV-2 complexes with single nanobodies Nb6 and Nb20, VHH E, a pair combination VHH E + …

Prenatal Diagnosis Of Maternal Serum From Mothers Carrying Β-Thalassemic Fetus, Yumna Fazal, Muhammad Zohaib, Basir Syed, Saqib H. Ansari, Zehra Hashim, Aftab Ahmed, Shamshad Zarina

Pharmacy Faculty Articles and Research

Background

Current study focused on discovering protein biomarkers from the maternal serum of β-thalassemic trait mothers carrying the normal fetus and β-thalassemic major fetus.

Method

Serum samples from β-thalassemic trait mothers carrying major (N=5) and normal fetuses (N=5) were studied. IVS1-5 thalassemia mutation was common among β-thalassemic trait mothers who were carrying homozygous β-thalassemic fetus (IVS1-5/ IVS1-5 mutation) or normal fetus (no mutation). We employed two-dimensional gel electrophoresis and mass spectrometric analysis to explore differentially expressed maternal serum proteins from thalassemia carrier couples having the same β-thalassemia mutation. Western blotting was performed for one of the identified proteins to validate …

The Concise Guide To Pharmacology 2021/22: Enzymes, Stephen Ph Alexander, Doriano Fabbro, Eamonn Kelly, Alistair Mathie, John A. Peters, Emma L. Veale, Jane F. Armstrong, Elena Faccenda, Simon D. Harding, Adam J. Pawson, Christopher Southan, James A. Davies, Detlan Boison, Kathryn Elisa Burns, Carmen Dessauer, Jürg Gertsch, Nuala Ann Helsby, Angela A. Izzo, Doris Koesling, Rennolds Ostrom, Nigel J. Pyne, Susan Pyne, Michael Russwurm, Roland Seifert, Johannes-Peter Stasch, Mario Van Der Stelt, Albert Van Der Vliet, Val Watts, Szu Shen Wong

Pharmacy Faculty Articles and Research

The Concise Guide to PHARMACOLOGY 2021/22 is the fifth in this series of biennial publications. The Concise Guide provides concise overviews, mostly in tabular format, of the key properties of nearly 1900 human drug targets with an emphasis on selective pharmacology (where available), plus links to the open access knowledgebase source of drug targets and their ligands (www.guidetopharmacology.org), which provides more detailed views of target and ligand properties. Although the Concise Guide constitutes over 500 pages, the material presented is substantially reduced compared to information and links presented on the website. It provides a permanent, citable, point-in-time record …

Design And Application Of Hybrid Cyclic-Linear Peptide-Doxorubicin Conjugates As A Strategy To Overcome Doxorubicin Resistance And Toxicity, Saghar Mozaffari, David Salehi, Parvin Mahdipoor, Richard Beuttler, Rakesh Tiwari, Hamidreza Montazeri Aliabadi, Keykavous Parang

Pharmacy Faculty Articles and Research

Doxorubicin (Dox) is used for breast cancer, leukemia, and lymphoma treatment as an effective chemotherapeutic agent. However, Dox use is restricted due to inherent and acquired resistance and an 8-fold increase in the risk of potentially fatal cardiotoxicity. Hybrid cyclic-linear peptide [R5K]W7A and linear peptide R5KW7A were conjugated with Dox through a glutarate linker to afford [R5K]W7A-Dox and R5KW7A-Dox conjugates to generate Dox derivatives. Alternatively, [R5K]W7C was conjugated with Dox via a disulfide linker to generate [R5K]W7C–S–S-Dox conjugate, where S–S is a disulfide bond. Comparative antiproliferative assays between conjugates [R5K]W7A-Dox, [R5K]W7C–S–S-Dox, linear R5KW7A-Dox, the corresponding physical mixtures of the peptides, …

Community Pharmacies, Drug Stores, And Antibiotic Dispensing In Indonesia: A Qualitative Study, Astri Ferdiana, Marco Liverani, Mishal Khan, Luh Putu Lila Wulandari, Yusuf Ari Mashuri, Neha Batura, Tri Wibawa, Shunmay Yeung, Richard Day, Stephen Jan, Virginia Wiseman, Ari Probandari

Community Health Sciences

Background: Inappropriate dispensing of antibiotics at community pharmacies is an important driver of antimicrobial resistance (AMR), particularly in low- and middle-income countries. Thus, a better understanding of dispensing practices is crucial to inform national, regional, and global responses to AMR. This requires careful examination of the interactions between vendors and clients, sensitive to the context in which these interactions take place.
Methods: In 2019, we conducted a qualitative study to examine antibiotic dispensing practices and associated drivers in Indonesia, where self-medication with antibiotics purchased at community pharmacies and drug stores is widespread. Data collection involved 59 in-depth interviews with staff …

Educational Attainment Of Same-Sex And Opposite-Sex Dizygotic Twins: An Individual-Level Pooled Study Of 19 Twin Cohorts, Keith E. Whitfield, Numerous Authors, See Full List Below

Office of the President Faculty Publications

Comparing twins from same- and opposite-sex pairs can provide information on potential sex differences in a variety of outcomes, including socioeconomic-related outcomes such as educational attainment. It has been suggested that this design can be applied to examine the putative role of intrauterine exposure to testosterone for educational attainment, but the evidence is still disputed. Thus, we established an international database of twin data from 11 countries with 88,290 individual dizygotic twins born over 100 years and tested for differences between twins from same- and opposite-sex dizygotic pairs in educational attainment. Effect sizes with 95% confidence intervals (CI) were estimated …

Computational Analysis Of Bshc, An Enzyme Responsible For Antibiotic Resistance In Firmicute Bacteria, Matthew R. Martin

Student Summer Scholars Manuscripts

Bacillithiol is a compound synthesized by certain gram-positive bacteria called firmicutes, such as B. Subtilis. This compound is used to protect the bacterium from oxidative stress and establish antibiotic resistance. There are three enzymes in the synthesis pathway of bacillithiol: BshA, BshB, and BshC¹.BshC, unlike the other two, has a potentially novel mechanism that is not yet well understood. This enzyme is a putative cysteine ligase, however the ligand that donates the cysteine is unknown. The structure of BshC has been previously solved and has a unique dumbbell shape suggesting a hinging motion. Previous Small Angle X-ray Scattering …

Emergence Of Cationic Polyamine Dendrimersomes: Design, Stimuli Sensitivity And Potential Biomedical Applications, Partha Laskar, Christine Dufès

School of Medicine Publications and Presentations

For decades, self-assembled lipid vesicles have been widely used in clinics as nanoscale delivery systems for various biomedical applications, including treatment of various diseases. Due to their core–shell architecture and versatile nature, they have been successfully used as carriers for the delivery of a wide range of therapeutic cargos, including drugs and nucleic acids, in cancer treatment. Recently, surface-modified polyamine dendrimer-based vesicles, or dendrimersomes, have emerged as promising alternatives to lipid vesicles for various biomedical applications, due to their ease of synthesis, non-immunogenicity, stability in circulation and lower size polydispersity. This mini-review provides an overview of the recent advances resulting …

Subtype-Selective Positive Modulation Of KCa 2 Channels Depends On The Ha/Hb Helices, Young-Woo Nam, Meng Cui, Naglaa Salem, Razan Orfali, Misa Nguyen, Grace Yang, Mohammad Asikur Rahman, Judy Lee, Miao Zhang

Pharmacy Faculty Articles and Research

Background and Purpose

In the activated state of small-conductance Ca2+-activated potassium (KCa 2) channels, calmodulin interacts with the HA/HB helices and the S4-S5 linker. CyPPA potentiates KCa 2.2a and KCa 2.3 channel activity but not the KCa 2.1 and KCa 3.1 subtypes.

Experimental Approach

Site-directed mutagenesis, patch-clamp recordings and in silico modeling were utilized to explore the structural determinants for the subtype-selective modulation of KCa 2 channels by CyPPA.

Key Results

Mutating residues in the HA (V420) and HB (K467) helices of KCa 2.2a channels to their equivalent residues in KCa 3.1 channels diminished the potency of CyPPA. CyPPA elicited …

No Ordinary Proteins: Adsorption And Molecular Orientation Of Monoclonal Antibodies, Ankit D. Kanthe, Andrew Ilott, Mary Krause, Songyan Zheng, Jinjiang Li, Wei Bu, Mrinal K. Bera, Binhua Lin, Charles Maldarelli, Raymond S. Tu

Publications and Research

The interaction of monoclonal antibodies (mAbs) with air/water interfaces plays a crucial role in their overall stability in solution. We aim to understand this behavior using pendant bubble measurements to track the dynamic tension reduction and x-ray reflectivity to obtain the electron density profiles (EDPs) at the surface. Native immunoglobulin G mAb is a rigid molecule with a flat, “Y” shape, and simulated EDPs are obtained by rotating a homology construct at the surface. Comparing simulations with experimental EDPs, we obtain surface orientation probability maps showing mAbs transition from flat-on Y-shape configurations to side-on or end-on configurations with increasing concentration. …

Environmental Equity And The Cosmetics Industry: The Effect Of Class Upon Toxic Exposure, Sean Storr '22

Student Scholarship

Cosmetic products in the United States are unregulated and oftentimes toxic. It is well established that the threats that cosmetics pose disproportionately harm women and women of color. However, when the hazards of the cosmetic industry have been analyzed, the relationship between toxic exposure and financial means has been largely omitted. In this study I evaluate the link between poverty and toxic burden through cosmetic products through literature review and a data analysis of pre-existing online databases. Through the use of the Campaign for Safe Cosmetics’ Red List and the Environmental Working Group’s Skin Deep database, I investigate whether cosmetic …

Dose Adjustment Of Antidiabetic Medications In Chronic Kidney Disease, Matthew Salvatore Snyder, Joshua Fogel, Svetlana Pyatigorskaya, Sofia Rubinstein

Publications and Research

Purpose: The purpose of this study is to identify whether Internal Medicine house-staff (IMHS) have awareness and knowledge about the correct dosage of antidiabetic medications for patients with chronic kidney disease (CKD), as dosing errors result in adverse patient outcomes for those with diabetes mellitus (DM) and CKD.

Methods: There were 353 IMHS surveyed to evaluate incorrect level of awareness of medication dose adjustment in patients with CKD (ILA) and incorrect level of knowledge of glomerular filtration rate level for medication adjustment (ILK-GFR) for Glipizide, Pioglitazone, and Sitagliptin.

Results: Lack of awareness and knowledge was high, with the highest for …

Uplc-Ms/Ms Analysis Of The Michaelis-Menten Kinetics Of Cyp3a-Mediated Midazolam 1′- And 4-Hydroxylation In Rat Brain Microsomes, Devaraj Venkatapura Chandrashekar, Barent Dubois, Reza Mehvar

Pharmacy Faculty Articles and Research

Midazolam (MDZ) is a short-acting benzodiazepine with rapid onset of action, which is metabolized by CYP3A isoenzymes to two hydroxylated metabolites, 1′-hydroxymidazolam and 4-hydroxymidazolam. The drug is also commonly used as a marker of CYP3A activity in the liver microsomes. However, the kinetics of CYP3A-mediated hydroxylation of MDZ in the brain, which contains much lower CYP content than the liver, have not been reported. In this study, UPLC-MS/MS and metabolic incubation methods were developed and validated for simultaneous measurement of low concentrations of both hydroxylated metabolites of MDZ in brain microsomes. Different concentrations of MDZ (1–500 µM) were incubated with …

Insights Into The Mechanisms Of Brain Endothelial Erythrophagocytosis, Jiahong Sun, Prema Vyas, Samar Mann, Annlia Paganini-Hill, Ane C. F. Nunes, Wei Ling Lau, David H. Cribbs, Mark J. Fisher, Rachita K. Sumbria

Pharmacy Faculty Articles and Research

The endothelial cells which form the inner cellular lining of the vasculature can act as non-professional phagocytes to ingest and remove emboli and aged/injured red blood cells (RBCs) from circulation. We previously demonstrated an erythrophagocytic phenotype of the brain endothelium for oxidatively stressed RBCs with subsequent migration of iron-rich RBCs and RBC degradation products across the brain endothelium in vivo and in vitro, in the absence of brain endothelium disruption. However, the mechanisms contributing to brain endothelial erythrophagocytosis are not well defined, and herein we elucidate the cellular mechanisms underlying brain endothelial erythrophagocytosis. Murine brain microvascular endothelial cells (bEnd.3 …

Anatomy And Physiology Preparatory Course Textbook (2nd Edition), Carlos Liachovitzky

Open Educational Resources

The goal of this preparatory textbook is to give students a chance to become familiar with some terms and some basic concepts they will find later on in the Anatomy and Physiology course, especially during the first few weeks of the course.

Organization and functioning of the human organism are generally presented starting from the simplest building blocks, and then moving into levels of increasing complexity. This textbook follows the same presentation. It begins introducing the concept of homeostasis, then covers the chemical level, and later on a basic introduction to cellular level, organ level, and organ system level. This …

In-Line Monitoring Of Sitagliptin Dissolution Profile From Tablets Utilizing An Eco-Friendly Potentiometric Sensor, Shereen Mowaka, Manar M. Elhassan, Amr M. Mahmoud, Maha A. Hegazy

Pharmacy

Sitagliptin, an oral antidiabetic drug, is an effective medication for lowering blood glucose level either as monotherapy or in combination with other antidiabetic drugs. This work aims for the fabrication of a potentiometric sensor for sitagliptin detection. The sensor was designed by doping the polyvinyl chloride polymeric ion-selective membrane with calix[4]arene as an ionophore which highly improved the linearity range (1 × 10−6—1 × 10−2 M), sensitivity, selectivity and limit of detection (6.3 × 10−7 M) compared to ionophore-free membrane. The method was then validated according to the International Council for Harmonization (ICH) guidelines. The sensor was successfully employed to …

July / August 2021, Randy Curry, Cindy Brooks

RURAL ROCKS

Rural Rocks, the Rural Health Network newsletter by the SWOSU College of Pharmacy.

Milk Exosomes: Nature's Abundant Nanoplatform For Theranostic Applications, Benilde Adriano, Nycol Cotto, Neeraj Chauhan, Meena Jaggi, Subhash C. Chauhan, Murali M. Yallapu

School of Medicine Publications and Presentations

Exosomes are a unique subpopulation of naturally occurring extracellular vesicles which are smaller intracellular membrane nanoparticle vesicles. Exosomes have proven to be excellent nanocarriers for carrying lipids, proteins, mRNAs, non-coding RNAs, and DNAs, and disseminating long-distance intercellular communications in various biological processes. Among various cell-line or biological fluid derived exosomes, milk exosomes are abundant in nature and exhibit many nanocarrier characteristics favorable for theranostic applications. To be an effective delivery carrier for their clinical translation, exosomes must inbuilt loading, release, targeting, and imaging/tracking characteristics. Considering the unmet gaps of milk exosomes in theranostic technology it is essential to focus the …

Suppression Of Dc-Sign And Gh Reveals Complex, Subset-Specific Mechanisms For Kshv Entry In Primary B Lymphocytes, Nancy Palmerin, Farizeh Aalam, Romina Nabiee, Murali Muniraju, Javier Gordon Ogembo, Jennifer Totonchy

Pharmacy Faculty Articles and Research

Kaposi sarcoma-associated herpesvirus (KSHV) is the causative agent of multiple cancers in immunocompromised patients including two lymphoproliferative disorders associated with KSHV infection of B lymphocytes. Despite many years of research into the pathogenesis of KSHV associated diseases, basic questions related to KSHV molecular virology remain unresolved. One such unresolved question is the cellular receptors and viral glycoproteins needed for KSHV entry into primary B lymphocytes. In this study, we assess the contributions of KSHV glycoprotein H (gH) and the cellular receptor DC-SIGN to KSHV infection in tonsil-derived B lymphocytes. Our results show that (1) neither KSHV-gH nor DC-SIGN are essential …

Dimeric Allostery Mechanism Of The Plant Circadian Clock Photoreceptor Zeitlupe, Francesco Trozzi, Feng Wang, Gennady M. Verkhivker, Brian D. Zoltowski, Peng Tao

Mathematics, Physics, and Computer Science Faculty Articles and Research

In Arabidopsis thaliana, the Light-Oxygen-Voltage (LOV) domain containing protein ZEITLUPE (ZTL) integrates light quality, intensity, and duration into regulation of the circadian clock. Recent structural and biochemical studies of ZTL indicate that the protein diverges from other members of the LOV superfamily in its allosteric mechanism, and that the divergent allosteric mechanism hinges upon conservation of two signaling residues G46 and V48 that alter dynamic motions of a Gln residue implicated in signal transduction in all LOV proteins. Here, we delineate the allosteric mechanism of ZTL via an integrated computational approach that employs atomistic simulations of wild type and …

Exposure To Endocrine Disrupting Chemicals (Edcs) And Cardiometabolic Indices During Pregnancy: The Home Study, Ann M. Vuong, Joseph M. Braun, Andreas Sjödin, Antonia M. Calafat, Kimberly Yolton, Bruce P. Lanphear, Aimin Chen

Public Health Faculty Publications

Background: Toxicology studies have identified pregnancy as a window of susceptibility for endocrine disrupting chemicals (EDCs) and cardiometabolic indices in women. No study in humans, however, has examined EDC mixtures and cardiometabolic indices during pregnancy. Methods: We used the Health Outcomes and Measures of the Environment (HOME) Study to examine whether bisphenol A (BPA), polybrominated diphenyl ethers (PBDEs), per- and polyfluoroalkyl substances (PFAS), and phthalates are associated with blood pressure, glucose, and lipids in 388 pregnant women. We measured PBDEs and PFAS in serum at 16 weeks gestation, while BPA and phthalate metabolites were quantified in urine at 16 and …

Transversus Abdominis Plane Block: A Scoping Review, Liam Maher, Leanne Orians, Gabrielle Pappas, Lanny Coker Dnsc, Crna

Doctor of Nursing Practice Projects

The purpose of this project is to provide an overview of the literature on the analgesic effects of transverse abdominal plane (TAP) block and its effectiveness in reducing opioid consumption.

Intraoperative Dexmedetomidine For Reduction Of Postoperative Delirium In The Elderly: A Scoping Review, Gregory B. Harris Bsn, Rn, Srna, Brooke N. Hatchell Bsn, Rn, Srna, Davelin D. Woodard Bsn, Rn, Srna, Dwayne Accardo Dnp, Aprn, Crna

Doctor of Nursing Practice Projects

Background/Purpose: Post-operative delirium leads to significant morbidity in elderly patients, yet there is no regimen to prevent POD. Opioid use in the elderly surgical population is of the most significant risk factors for developing POD. The purpose of this scoping review is to recognize that Dexmedetomidine mitigates cognitive dysfunction secondary to acute pain and the use of narcotic analgesia by decreasing the amount of norepinephrine (an excitatory neurotransmitter) released during times of stress. This mechanism of action also provides analgesia through decreased perception and modulation of pain.

Methods: The authors developed eligibility criteria for inclusion of articles and performed a …

Lipoprotein-Induced Increases In Cholesterol And 7-Ketocholesterol Result In Opposite Molecular-Scale Biophysical Effects On Membrane Structure, Manuela A.A. Ayee, Irena Levitan

Faculty Work Comprehensive List

Under hypercholesterolemic conditions, exposure of cells to lipoproteins results in a subtle membrane increase in the levels of cholesterol and 7-ketocholesterol, as compared to normal conditions. The effect of these physiologically relevant concentration increases on multicomponent bilayer membranes was investigated using coarse-grained molecular dynamics simulations. Significant changes in the structural and dynamic properties of the bilayer membranes resulted from these subtle increases in sterol levels, with both sterol species inducing decreases in the lateral area and inhibiting lateral diffusion to varying extents. Cholesterol and 7-ketocholesterol, however, exhibited opposite effects on lipid packing and orientation. The results from this study indicate …

Pain Control: Opioid Vs. Nonopioid Analgesia During The Immediate Postoperative Period, Shamsie M. Lumpkin Bsn, Srna, Isaac W. Parrish Bsn, Srna, Austin S. Terrell Bsn, Srna, Dwayne S. Accardo Dnp, Aprn, Crna

Doctor of Nursing Practice Projects

Background Opioid analgesia has become the mainstay for acute pain management in the postoperative setting. However, the use of opioid medications comes with significant risks and side effects. Due to increasing numbers of prescriptions to those with chronic pain, opioid medications have become more expensive while becoming less effective due to the buildup of patient tolerance. The idea of opioid-free analgesic techniques has rarely been breached in many hospitals. Emerging research has shown that opioid-sparing approaches have resulted in lower reported pain scores across the board, as well as significant cost reductions to hospitals and insurance agencies. In addition to …

Human Oncoprotein 5mp Suppresses General And Repeat-Associated Non-Aug Translation Via Eif3 By A Common Mechanism, Chingakham Ranjit Singh, M. Rebecca Glineburg, Chelsea Moore, Naoki Tani, Rahul Jaiswal, Ye Zou, Eric Aube, Sarah Gillaspie, Mackenzie Thornton, Ariana Cecil, Madelyn Hilgers, Azuma Takasu, Izumi Asano, Masayo Asano, Carlos R. Escalante, Akira Nakamura, Peter K. Todd, Katsura Asano

Biology, Chemistry, and Environmental Sciences Faculty Articles and Research

eIF5-mimic protein (5MP) is a translational regulatory protein that binds the small ribosomal subunit and modulates its activity. 5MP is proposed to reprogram non-AUG translation rates for oncogenes in cancer, but its role in controlling non-AUG initiated synthesis of deleterious repeat-peptide products, such as FMRpolyG observed in fragile-X-associated tremor ataxia syndrome (FXTAS), is unknown. Here, we show that 5MP can suppress both general and repeat-associated non-AUG (RAN) translation by a common mechanism in a manner dependent on its interaction with eIF3. Essentially, 5MP displaces eIF5 through the eIF3c subunit within the preinitiation complex (PIC), thereby increasing the accuracy of initiation. …