Molecular Biology Commons^™

Generation Of Mycobacterium Smegmatis Model Systems For Testing Inhibitors Of The Mycobactin Siderophore Of Mycobacterium Tuberculosis, Gabrielle A. Germain

Dissertations, Theses, and Capstone Projects

Mycobacterium tuberculosis (Mtb) is the pathogenic bacterium causative of tuberculosis. According to the 2021 World Health Organization (WHO) Global Tuberculosis (TB) Report, there were approximately 5.8 million TB cases in 2020, and 1.3 million TB deaths among HIV negative people in that year. The rise of multi-drug resistant Mtb strains has increased the need for more potent microbials against this pathogen. Biosynthesis of iron scavenging molecules, known as siderophores (e.g., mycobactin and carboxymycobactin), has been identified as a potential drug target candidate since iron acquisition has been directly linked to the survival and virulence of Mtb. Salicyl-AMS (Sal-AMS) is …

Transcriptional Mechanisms Of Neuroprotection In Excitotoxicity Driven Neurodegeneration In C. Elegans, Zelda Z. Mendelowitz

Dissertations, Theses, and Capstone Projects

Excitotoxicity is notorious for triggering neuronal cell death in both developmental and adult-onset neurodegenerative diseases. In excitotoxicity, excessive concentrations of Glutamate in the synapse overstimulate Glutamate Receptors (GluRs) on postsynaptic neurons. While GluR mediated degenerative mechanisms remain obscure, GluR activation was surprisingly found to also have a neuroprotective effect through activation of specific transcriptional programs. To identify evolutionarily conserved transcriptional programs in neuroprotection we use a C. elegans model of excitotoxic necrosis (glt-3;nuIs5). We have identified that non-canonical activation of the transcription factor CRH-1/CREB mediates neuroprotection in our excitotoxicity model. We found the Histone Acetyl Transferase, MYS-1/KAT6, and the neuronal …

Signature Peptide Identification For Body Fluids In Sexual Assault Cases By Liquid Chromatography Tandem Mass Spectrometry (Lc-Ms/Ms), Kelci Somers

Student Theses

Body fluids contain proteins that perform functions specific to different types of body fluids. Therefore, the detection of signature peptides for these proteins can potentially identify a body fluid in a forensic investigation. This project aimed to validate a method to detect signature peptides in body fluids commonly found in sexual assault cases by LC-MS/MS. Signature peptides for semen and saliva fluids were combined with two signature peptides for vaginal fluids. Samples created using two donors each for saliva, semen, and vaginal fluids were extracted using a trypsin digest, with separation of the protein and DNA fractions. The LC-MS/MS was …

Elucidating Mechanisms Of Biofluorescence And Bioluminescence In Marine Organisms, Andrew M. Guarnaccia

Dissertations, Theses, and Capstone Projects

Biofluorescence and bioluminescence are two methods of light emission that entail separate mechanisms of action but end at the same process: a colorful display that have tremendous ecological and behavioral benefits, whether it be used to communicate with conspecifics, camouflage into a multicolored background, attract unsuspecting prey, or alert others to a predator. In biofluorescence, higher-energy, shorter wavelength light is absorbed then re-emitted as lower-energy, longer-wavelength light. Bioluminescence on the other hand entails a chemical reaction in which a small molecule is oxidized by an enzyme, creating a high-energy intermediate that sheds the excess energy in the form of visible …

Cdc6 Is Sequentially Regulated By Pp2a-Cdc55, Cdc14, And Sic1 For Origin Licensing In S. Cerevisiae, Jasmin Philip

Dissertations, Theses, and Capstone Projects

Control of DNA replication is critical for progression of the cell cycle and genomic stability. Cyclin-dependent kinases (CDKs) coordinate numerous phosphorylation events to accomplish two biological tasks for all living organisms: DNA replication and cell division. One CDK, Cyclin-Cdc28, is responsible for cell cycle progression in budding yeast. DNA replication requires a stepwise assembly of the pre-replicative complex on DNA, including Orc1-6, Cdc6, Cdt1 and Mcm2-7, during M-G1 phase. Cdc6 contains eight Cdc28 consensus sites, SP or TP motifs. Clb5-Cdc28 phosphorylates Cdc6-T7 to recruit Cks1, the Cdc28 phospho-adaptor, for subsequent multisite phosphorylation during S phase. There are two phospho-degrons at …

Eukaryotic Initiation Factor 4e (Eif4e) In Complex With Eif4e Binding Protein 1 (4e-Bp1) Binds With Higher Affinity To M7gpppn Cap Of A Subset Of Human Mrnas, Izza F. Nawaz

Theses and Dissertations

Fluorescence anisotropy binding assays were used to analyze the binding of eIF4E in complex with 4E-BP1 onto the 5’ m7G cap of a subset of mRNA that are known to carry cap-independent translation. These studies suggest that 4E-BP1 increases eIF4E binding affinity to 5’cap of both FGF-9 and HIF-1𝝰.

Scientific Development Of An Integrated Workflow For Latent Print, Questioned Document, And Dna Processing Of Paper Evidence, Ashley Morgan

Dissertations, Theses, and Capstone Projects

Touch paper evidence could be the source of probative human DNA but recovery is challenging and forensic laboratories instead prioritize processing by the Latent Print and Questioned Document disciplines. Recent advances in DNA collection methods and the increased sensitivity of STR typing kits have improved success rates for DNA testing of paper evidence; but prior to implementing DNA collection, laboratories have to decide in which order to examine paper for the different types of forensic evidence. This thesis developed and tested a multi-discipline workflow for processing paper evidence by DNA, Latent Prints and Questioned Documents experts. Preliminary sampling studies indicated …

Paddling Along The Voltage Gated Sodium Channel Galaxy With Sea Anemone Toxins: Structural Studies Of The Interaction Between The Paddle Motif From Nav1.5div And Sea Anemone Toxin, Adel K. Hussein

Dissertations, Theses, and Capstone Projects

Voltage gated sodium channels (VGSC) are membrane proteins that serve an important function in the central nervous system (CNS), peripheral nervous system (PNS), and cardiac muscles amongst others. The main function of VGSC is in the propagation of electrical signals by depolarizing excitable cells. Nine mammalian VGSC subtypes have been characterized, Na_V1.1 – Na_V1.9, that are expressed in a tissue specific manner, each with unique gating properties. Numerous diseases have been linked to defects in VGSC including epilepsy, mental retardation, long QT syndrome, and Brugada disease. Furthermore, these channels are one of the primary targets of …

Glycocalyx Mechanotransduction Mechanisms Are Involved In Renal Cancer Metastasis, Heriberto Moran, Limary M. Cancel, Peigen Huang, Sylvie Roberge, Tuoye Xu, John M. Tarbell, Lance L. Munn

Publications and Research

Mammalian cells, including cancer cells, are covered by a surface layer containing cell bound proteoglycans, glycoproteins, associated glycosaminoglycans and bound proteins that is commonly referred to as the glycocalyx. Solid tumors also have a dynamic fluid microenvironment with elevated interstitial flow. In the present work we further investigate the hypothesis that interstitial flow is sensed by the tumor glycocalyx leading to activation of cell motility and metastasis. Using a highly metastatic renal carcinoma cell line (SN12L1) and its low metastatic counterpart (SN12C) we demonstrate in vitro that the small molecule Suberoylanilide Hydroxamic Acid (SAHA) inhibits the heparan sulfate synthesis enzyme …

Reproducibility Of Individual Dna Deposits Detected Through Cellular Fluorescence, Natalee Small-Davidson

Student Theses

Contact traces are an important part of DNA casework, but the probative value of any identified associations depends on the possibility of passive transfer. There is known individual variation in DNA left behind during contact, this DNA shedding propensity has an effect on whose DNA is detected. This study evaluated this variability using a cell staining approach. Volunteers were asked to deposit a fingerprint on a clean glass slide, then wash their hands and deposit a second fingerprint after a 30-minute wait without touching anything. Three sets of samples were collected over three consecutive weeks. Fingerprints were stained with a …

High-Resolution Cryo-Electron Microscopy Structure Of Photosystem Ii From The Mesophilic Cyanobacterium, Synechocystis Sp. Pcc 6803, Christopher J. Gisriel, Jimin Wang, Jinchan Liu, David A. Flesher, Krystle M. Reiss, Hao-Li Huang, Ke R. Yang, William H. Armstrong, M. R. Gunner, Victor S. Batista, Richard J. Debus, Gary W. Brudvig

Publications and Research

Photosystem II (PSII) enables global-scale, light-driven water oxidation. Genetic manipulation of PSII from the mesophilic cyanobacterium Synechocystis sp. PCC 6803 has provided insights into the mechanism of water oxidation; however, the lack of a highresolution structure of oxygen-evolving PSII from this organism has limited the interpretation of biophysical data to models based on structures of thermophilic cyanobacterial PSII. Here, we report the cryo-electron microscopy structure of PSII from Synechocystis sp. PCC 6803 at 1.93-Å resolution. A number of differences are observed relative to thermophilic PSII structures, including the following: the extrinsic subunit PsbQ is maintained, the C terminus of the …

Cryptococcus Neoformans Melanization Incorporates Multiple Catecholamines To Produce Polytypic Melanin, Rosanna P. Baker, Christine Chrissian, Ruth E. Stark, Arturo Casadevall

Publications and Research

Melanin is a major virulence factor in pathogenic fungi that enhances the ability of fungal cells to resist immune clearance. Cryptococcus neoformans is an important human pathogenic fungus that synthesizes melanin from exogenous tissue catecholamine precursors during infection, but the type of melanin made in cryptococcal meningoencephalitis is unknown. We analyzed the efficacy of various catecholamines found in brain tissue in supporting melanization using animal brain tissue and synthetic catecholamine mixtures reflecting brain tissue proportions. Solid-state NMR spectra of the melanin pigment produced from such mixtures yielded more melanin than expected if only the preferred constituent dopamine had been incorporated, …

Discovery Of Phosphotyrosine-Binding Oligopeptides With Supramolecular Target Selectivity, Ana S. Pina, Leonor Morgado, Krystyna L. Duncan, Sara Carvalho, Henrique F. Carvalho, Armenio J. M. Barbosa, Beatriz De P. Mariz, Ines P. Moreira, Daniela Kalafatovic, Bruno M. Morais Faustino, Vishal Narang, Tong Wang, Charalampos G. Pappas, Isabel Ferreira, A. Cecılia A. Roque, Rein V. Ulijn

Advanced Science Research Center

We demonstrate phage-display screening on self-assembled ligands that enables the identification of oligopeptides that selectively bind dynamic supramolecular targets over their unassembled counterparts. The concept is demonstrated through panning of a phage-display oligopeptide library against supramolecular tyrosine-phosphate ligands using 9-fluorenylmethoxycarbonyl-phenylalanine-tyrosine-phosphate (Fmoc-FpY) micellar aggregates as targets. The 14 selected peptides showed no sequence consensus but were enriched in cationic and proline residues. The lead peptide, KVYFSIPWRVPM-NH2 (P7) was found to bind to the Fmoc-FpY ligand exclusively in its self-assembled state with KD = 74 ± 3 μM. Circular dichroism, NMR and molecular dynamics simulations revealed that the peptide interacts with Fmoc-FpY …

Living With A Giant, Flowering Parasite: Metabolic Differences Between Tetrastigma Loheri Gagnep. (Vitaceae) Shoots Uninfected And Infected With Rafflesia (Rafflesiaceae) And Potential Applications For Propagation, Jeanmaire Molina, Dejan Nikolic, Jashvanth Raaj Jeevarathanam, Rinat Abzalimov, Eun‑Jung Park, Ronniel Pedales, Elmer‑Rico E. Mojica, Danilo Tandang, William Mclaughlin, Kyle Wallick, James Adams, Ari Novy, Susan K. Pell, Richard B. Van Breemen, John M. Pezzuto

Advanced Science Research Center

Main conclusion: Metabolites in Rafflesia-infected and non-infected Tetrastigma were compared which may have applications in Rafflesia propagation. Benzylisoquinoline alkaloids, here reported for the first time in Vitaceae, were abundant in non-infected shoots and may be a form of defense. In Rafflesia-infected shoots, oxylipins, which mediate immune response, were elevated.

Endemic to the forests of Southeast Asia, Rafflesia (Rafflesiaceae) is a genus of holoparasitic plants producing the largest flowers in the world, yet completely dependent on its host, the tropical grape vine, Tetrastigma. Rafflesia species are threatened with extinction, making them an iconic symbol of plant conservation. Thus …

Structure Of A Monomeric Photosystem Ii Core Complex From A Cyanobacterium Acclimated To Far-Red Light Reveals The Functions Of Chlorophylls D And F, Christopher J. Gisriel, Gaozhong Shen, Ming-Yang Ho, Vasily Kurashov, David A. Flesher, Jimin Wang, William H. Armstrong, John H. Golbeck, Marilyn R. Gunner, David J. Vinyard, Richard J. Debus, Gary W. Brudvig, Donald A. Bryant

Publications and Research

Far-red light (FRL) photoacclimation in cyanobacteria provides a selective growth advantage for some terrestrial cyanobacteria by expanding the range of photosynthetically active radiation to include far-red/near-infrared light (700–800 nm). During this photoacclimation process, photosystem II (PSII), the water:plastoquinone photooxidoreductase involved in oxygenic photosynthesis, is modified. The resulting FRL-PSII is comprised of FRL-specific core subunits and binds chlorophyll (Chl) d and Chl f molecules in place of several of the Chl a molecules found when cells are grown in visible light. These new Chls effectively lower the energy canonically thought to define the “red limit” for light required to drive photochemical …

Cryo-Em Structure Of Mechanosensitive Channel Ynai Using Sma2000: Challenges And Opportunities, Claudio Catalano, Danya Ben-Hail, Weihua Qiu, Paul Blount, Amedee Des Georges, Youzhong Guo

Publications and Research

Mechanosensitive channels respond to mechanical forces exerted on the cell membrane and play vital roles in regulating the chemical equilibrium within cells and their environment. Highresolution structural information is required to understand the gating mechanisms of mechanosensitive channels. Protein-lipid interactions are essential for the structural and functional integrity of mechanosensitive channels, but detergents cannot maintain the crucial native lipid environment for purified mechanosensitive channels. Recently, detergent-free systems have emerged as alternatives for membrane protein structural biology. This report shows that while membrane-active polymer, SMA2000, could retain some native cell membrane lipids on the transmembrane domain of the mechanosensitive-like YnaI channel, …

A Conserved Structural Role For The Walker-A Lysine In P-Loop Containing Kinases, Fatlum Hajredini, Ranajeet Ghose

Publications and Research

Bacterial tyrosine kinases (BY-kinases) and shikimate kinases (SKs) comprise two structurally divergent P-loop containing enzyme families that share similar catalytic site geometries, most notably with respect to their Walker-A, Walker-B, and DxD motifs. We had previously demonstrated that in BY-kinases, a specific interaction between the Walker-A and Walker-B motifs, driven by the conserved “catalytic” lysine housed on the former, leads to a conformation that is unable to efficiently coordinate Mg²⁺•ATP and is therefore incapable of chemistry. Here, using enhanced sampling molecular dynamics simulations, we demonstrate that structurally similar interactions between the Walker-A and Walker-B motifs, also mediated by …

Aurora Kinase A Inhibition Reverses The Warburg Effect And Elicits Unique Metabolic Vulnerabilities In Glioblastoma, Trang T. T. Nguyen, Enyuan Shang, Chang Shu, Sungsoo Kim, Angeliki Mela, Nelson Humala, Aayushi Mahajan, Hee Won Yang, Hasan Orhan Akman, Catarina M. Quinzii, Guoan Zhang, Mike-Andrew Westhoff, Georg Karpel-Massler, Jeffrey N. Bruce, Peter Canoll, Markus D. Siegelin

Publications and Research

Aurora kinase A (AURKA) has emerged as a drug target for glioblastoma (GBM). However, resistance to therapy remains a critical issue. By integration of transcriptome, chromatin immunoprecipitation sequencing (CHIP-seq), Assay for Transposase-Accessible Chromatin sequencing (ATAC-seq), proteomic and metabolite screening followed by carbon tracing and extracellular flux analyses we show that genetic and pharmacological AURKA inhibition elicits metabolic reprogramming mediated by inhibition of MYC targets and concomitant activation of Peroxisome Proliferator Activated Receptor Alpha (PPARA) signaling. While glycolysis is suppressed by AURKA inhibition, we note an increase in the oxygen consumption rate fueled by enhanced fatty acid oxidation (FAO), which was …

Study Of The Gain-Of-Function Mutant P53 And Parp1 In Triple-Negative Breast Cancer, Devon Lundine

Dissertations, Theses, and Capstone Projects

Cancer cells often lose expression of the p53 protein or express mutant forms of p53. Some of these mutant p53 proteins, called gain-of-function mutant p53, have gained oncogenic functions. Previously, our group observed mutant p53 R273H interacts with replicating DNA and upregulates the chromatin localization of several DNA replication factors including PCNA, MCM2-7, and PARP1 (termed the mtp53-PARP-MCM axis). In this thesis, we explore the contribution of mutant p53 and PARP1 in castration-resistant prostate cancer (mutant p53 P223L and V274F) and triple-negative breast cancer (mutant p53 R273H). In the castration-resistant prostate cancer cell line DU145, we examine two mutant p53 …

Understanding The Influence Of Zinc On Grain Cadmium Accumulation And Bioaccessibility In Rice, Michael A. Tavarez

Dissertations, Theses, and Capstone Projects

The effect of cadmium and zinc on mineral concentrations in three cultivars of rice

Interactions between the essential mineral zinc (Zn) and the toxic heavy metal cadmium (Cd) play an important role in regulating transport of both minerals to rice grains. Understanding these interactions is crucial for limiting cadmium and increasing zinc transfer to the food chain. Previous studies on the matter have had conflicting results suggesting synergistic and antagonistic relationships between the minerals. The goal of this work was to identify the effect of external cadmium and zinc on the uptake and translocation of both minerals from roots to …

The Structural And Functional Role Of Photosensing In Rgs-Lov Proteins, Zaynab Jaber

Dissertations, Theses, and Capstone Projects

Light provides organisms with energy and spatiotemporal information. To survive and adapt, organisms have developed the ability to sense light to drive biochemical effects that underlie vision, entrainment of circadian rhythm, stress response, virulence, and many other important molecularly driven responses. Blue-light sensing Light-Oxygen-Voltage (LOV) domains are ubiquitous across multiple kingdoms of life and modulate various physiological events via diverse effector domains. Using a small molecule flavin chromophore, the LOV domain undergoes light-dependent structural changes leading to activation or repression of these catalytic and non-catalytic effectors. In silico analyses of high-throughput genomic sequencing data has led to the marked expansion …

The Role Of Estrogen Receptor Alpha In Regulating Messenger Rna 3’ End Processing And Controlling Gene Expression In Breast Cancer Cells, Sophia Varriano

Dissertations, Theses, and Capstone Projects

Estrogen signaling regulates various physiological processes within the female reproductive, cardiovascular, immune, and central nervous systems and is predominantly mediated by estrogen receptors (ER), ERα and ERβ. Transcriptional regulation by ERs has been widely studied, where activated ERs bind either directly to target genes through binding to estrogen response elements or indirectly through interacting with other proteins, resulting in changes in gene expression. However, the potential role of factors involved in the estrogen signaling pathway in posttranscriptional regulation has not been extensively documented. As 70-80% of breast cancers (BCs) are identified as ER(+), studying how these factors, particularly ERα, regulates …

Dual Control Of One Component Signaling: Mechanistic And Structural Insights Into El222 Active States, Uthama Phani R. Edupuganti

Dissertations, Theses, and Capstone Projects

Photoreceptors play a crucial role in signal transduction as specialized proteins which sense light as environmental stimuli and transduce the signal to control of downstream functions. Here we focus our attention on one class of these proteins, the Light-Oxygen-Voltage (LOV) domain, which is sensitive to blue light via an internally-bound flavin chromophore. Since their initial discovery in plant phototropins, many details of their photochemistry, chromophore interactions, and use with a diverse set of functional effectors have been described. However, several key details, especially a comprehensive understanding of signaling mechanism and its regulation, still remain elusive due in part to the …

Oxydifficidin-Producing Bacillus Presents Novel Antimicrobial Activity Against Neisseria Gonorrhoeae Involving The Deda Protein, Jingbo Kan

Dissertations, Theses, and Capstone Projects

Bacterial human pathogens cause severe infectious diseases which are the second most common cause of death next to cancer and cardiovascular diseases in the world, especially in developing countries. Gonorrhea particularly, is the second most common sexually transmitted infection (STI) which is caused by the microorganism Neisseria gonorrhoeae (GC). Centers for Disease Control and Prevention (CDC) estimates that more than 1.6 million new gonorrhea cases emerged in USA in 2018 (“Detailed STD Facts - Gonorrhea” n.d.). Also, the WHO (World Health Organization) shows that gonorrhea is the most antibiotic resistant STI (“PAHO/WHO | Gonorrhea” n.d.), highlighting the shortage of efficient …

Decoding The Roles Of Astrocytes And Hedgehog Signaling In Medulloblastoma, Terence Teixeira Duarte, Silvia Aparecida Teixeira, Luis Gonzalez-Reyes, Rui Manuel Reis

Publications and Research

The molecular evolution of medulloblastoma is more complex than previously imagined, as emerging evidence suggests that multiple interactions between the tumor cells and components of the tumor microenvironment (TME) are important for tumor promotion and progression. The identification of several molecular networks within the TME, which interact with tumoral cells, has provided new clues to understand the tumorigenic roles of many TME components as well as potential therapeutic targets. In this review, we discuss the most recent studies regarding the roles of astrocytes in supporting sonic hedgehog (SHH) subgroup medulloblastoma (MB) and provide an overview of MB progression through SHH …

Protein Motifs For Proton Transfers That Build The Transmembrane Proton Gradient, Divya Kaur, Umesh Khaniya, Yingying Zhang, M. R. Gunner

Publications and Research

Biological membranes are barriers to polar molecules, so membrane embedded proteins control the transfers between cellular compartments. Protein controlled transport moves substrates and activates cellular signaling cascades. In addition, the electrochemical gradient across mitochondrial, bacterial and chloroplast membranes, is a key source of stored cellular energy. This is generated by electron, proton and ion transfers through proteins. The gradient is used to fuel ATP synthesis and to drive active transport. Here the mechanisms by which protons move into the buried active sites of Photosystem II (PSII), bacterial RCs (bRCs) and through the proton pumps, Bacteriorhodopsin (bR), Complex I and Cytochrome …

Mitochondrial Distribution Of Glycine Receptors In Motor Neuron Cell Lines, Katsiaryna Milashevich

Student Theses and Dissertations

Although non-essential, glycine plays an important role in major metabolic reactions and is most known for its anti-inflammatory effects. An accumulation of contemporary research has shown that glycine is able to stabilize membrane potential using glycine receptors at the cellular level and to protect mitochondrial function directly, whether it is from inflammation, heavy metal poisoning, or ischemia-induced neuroinflammation. In this research, the existence of a hypothetical mitochondrial glycine receptor is examined. Immunofluorescence imaging was used to examine the presence of the glycine receptor subunits alpha 1 and alpha 2 in both non- differentiated and differentiated neuroblastoma cell lines. The preliminary …

Determination Of Human Shedding Propensity Based On Str Results, Genevieve Trapani

Student Theses

Trace DNA evidence may be discovered at a crime scene after having been deposited by a person of interest via active or passive transfer. Based on previous studies, passive transfer of one’s DNA is influenced by their shedding propensity, or probability of depositing a detectable amount of DNA through touch. Determining the shedding propensity of a person of interest can aid in trace DNA interpretation in forensic casework. This study explored STR profile quality and the presence of a DNA mixture for different skin surface locations, including fingertips before and after handwashing. As expected, unwashed fingers showed a higher prevalence …

Lighting The Way: Recent Insights Into The Structure And Regulation Of Phototropin Blue Light Receptors, Jaynee E. Hart, Kevin H. Gardner

Publications and Research

The phototropins (phots) are light-activated kinases that are critical for plant physiology and the many diverse optogenetic tools that they have inspired. Phototropins combine two bluelight- sensing Light–Oxygen–Voltage (LOV) domains (LOV1 and LOV2) and a C-terminal serine/threonine kinase domain, using the LOV domains to control the catalytic activity of the kinase. While much is known about the structure and photochemistry of the light-perceiving LOV domains, particularly in how activation of the LOV2 domain triggers the unfolding of alpha helices that communicate the light signal to the kinase domain, many questions about phot structure and mechanism remain. Recent studies have made …

Direct Recruitment Of Eif4gi And/Dap5 To The 5' Utr Of A Subset Of Human Mrna Drives Their Cap-Independent Translation, Solomon A. Haizel

Dissertations, Theses, and Capstone Projects

During unfavorable cellular conditions (e.g., tumor hypoxia, viral infection, nutrient deprivation, etc.), the canonical, cap-dependent translation initiation pathway in human cells is suppressed by sequestration of the cap-binding protein, eukaryotic initiation factor(eIF) 4E, by 4E-binding proteins. Circumvention of cap-dependent translation shutdown has been linked to tumor development and cancer progression. The stress-induced repression of cap-dependent translation has also been correlated with increased eIF4GI and its homolog, Death Associated Protein 5 (DAP5) expression levels, suggesting these factors have a role in cap-independent translation. Despite several evidence pointing towards a link upregulation of eIF4GI and /DAP5 levels during stress conditions, and the …