Biochemistry, Biophysics, and Structural Biology Commons^™

Characterizing 3-O-Sulfation-Induced Novel Compact Topologies In Heparan Sulfate And Their Interactions With Proteins, Samuel Holmes

Theses and Dissertations

Heparan sulfate (HS) is highly-charged, linear polysaccharide that interacts with numerous proteins in humans as consituents of proteoglycans. The action of sulfotransferase enzymes during the biosynthesis of HS can generate a combinatorially massive library of differentially sulfated sequences. Furthermore, the number and position of these sulfate groups are key to their biological activity, modulating their selectivities for certain proteins at the cell surface or ECM. The installation of a sulfate on the C3 hydroxyl of a glucosamine residue in HS represents the rarest of the sulfations, despite the HS 3-O-sulfotransferase (3OST) family being the most diverse of the other sulfotransferases. …

The Effect Of Alkalinity On Lampricide Effectiveness And Gill Physiology In Invasive Sea Lamprey (Petromyzon Marinus), Alexandre J. Walsh

Theses and Dissertations (Comprehensive)

The pesticides, 3-trifluoromethyl-4-nitrophenol (TFM) and niclosamide are used to control populations of invasive sea lamprey (Petromyzon marinus) in the Laurentian Great Lakes of North America. Added to streams infested with larval sea lamprey, the effectiveness of these pesticides, commonly called lampricides, are strongly influenced by water pH, with greater toxicity for both TFM and niclosamide in lower pH than higher pH water. However, the TFM and niclosamide sensitivity of sea lamprey are also greater in poorly buffered, low alkalinity water than in high alkalinity water but it is unclear why. One goal of my thesis was to propose …

Characterization Of The Clostridioides Difficile Glycosyl Hydrolase Ccsz, Brian Lowrance

Theses and Dissertations (Comprehensive)

Bacteria inhabit many of the harshest environments on Earth; persisting and thriving in conditions thought to be unsuitable for life. One common strategy to withstand these environments is the formation of a biofilm. Biofilm composition varies greatly, depending on the underlying community that produces it. Cellulose, a polymer consistently prevalent in biofilms, has been identified as a virulence factor in many pathogens and is suspected to be involved in pathogenesis by Clostridioides difficile. C. difficile is the #1 cause of hospital acquired diarrhea, which can range from mild to life-threatening infections. Biofilm formation is hypothesized to be involved in …

Natural Variation In Temperature-Modulated Immunity To Pseudomonas Syringae Pv. Tomato (Pst Dc3000) In Arabidopsis Thaliana Plants, Christina A. M. Rossi

Theses and Dissertations (Comprehensive)

Studies conducted on the model plant-pathogen system Arabidopsis thaliana-Pseudomonas syringae pv. tomato (Pst) showed that elevated temperature suppresses the pathogen-induced production of salicylic acid (SA), which is a key plant defence hormone. This increased host vulnerability at higher temperatures is due to downregulated expression of CALMODULIN BINDING PROTEIN 60-LIKE G (CBP60g) and SYSTEMIC ACQUIRED RESISTANCE DEFICIENT 1 (SARD1), which encode master regulators of SA production. Collectively, these previous studies only focused on one natural accession of Arabidopsis called Columbia-0 (Col-0). However, the intraspecific variation in Arabidopsis immunity phenotypes under elevated temperature remains unknown. To fill this critical knowledge gap, my …

Functional Residues Of Cjpata, Robert Lamont

Theses and Dissertations (Comprehensive)

Antibiotic resistance in pathogenic bacteria continues to challenge clinicians and threaten the lives of infected individuals. For this reason, new classes of antibiotics or new targets for antibiotic therapy are needed to circumvent this global health crisis. In Gram-negative bacteria, the enzymes peptidoglycan O-acetyltransferase A and B (PatA and PatB), are responsible for adding acetyl groups to the C-6 hydroxyl group of N-acetyl muramic acid (MurNAc) in peptidoglycan (PG). These acetyl groups are responsible for inhibiting the activity of lysozyme from host organisms that hydrolyze the β1-4 glycosidic linkage between MurNAc and N-acetylglucosamine (GlcNAc). The acetyl groups …

Exploring The Membrane Protein And Peptide Interactions Of Mitochondrial And Bacterial Lipid Systems, George Saudan

Theses and Dissertations (Comprehensive)

This study aims to expand the understanding of interactions between membrane lipids and proteins, and relate it to their biological functions in two experimental systems. The first system focuses on the interaction and conformation of a membrane protein Uncoupling Protein 4 (UCP4) in mitochondrial inner membrane lipids, in the absence and presence of cardiolipin; a lipid specific to mitochondrial inner membranes. The second system considers the interaction and conformation of a cell penetrating peptide, Penetratin, which can interact with both mammalian and bacterial cells. A N- and C-termini protected form of this 16-meric peptide (Pen2) was used to explore its …

A Biophysical Approach To Modeling Elevational Range Shifts In Colorado Mammal Communities, Ryan T. Mahar

Graduate Student Theses, Dissertations, & Professional Papers

Species geographic ranges are shifting in the face of contemporary climate warming, and documenting range shifts is crucial to our understanding of the underlying drivers mediating movement in geographic range limits. Studies on elevational range shifts with climate change are beginning to accrue within the literature, though observed shifts are idiosyncratic and difficult to predict. Some species may respond to warming temperatures by shifting their range limits upslope, where temperatures are cooler owing to the adiabatic lapse rate. However, species may also respond to warming temperatures in an elevation-dependent manner: if changes in snow depth expose overwintering organisms to colder …

Interactions Of Amyloid Peptides With Lipid Membranes, Yanxing Yang

Dissertations

The aggregation of amyloid proteins into fibrils is a hallmark of several diseases including Alzheimer’s (AD), Parkinson’s, and Type II diabetes. This aggregation process involves the formation of small size oligomers preceding the formation of insoluble fibrils. Recent studies have shown that these oligomers are more likely to be responsible for cell toxicity than fibrils. A possible mechanism of toxicity involves the interaction of oligomers with the cell membrane compromising its integrity. In particular, oligomers may form pore-like structures in the cell membrane affecting its permeability or they may induce lipid loss via a detergent-like effect. This dissertation aims to …

Phytochemical Constituents, Haematological Activities And Gc-Ms Analysis Of Isolated Oil Of Rosary Pea (Abrus Precatorius) In Wistar Rat Fed With High Lipid Diet, Osaro Iyekowa, Opara V Ndubuisi

Tanzania Journal of Science

The study is aimed at investigating the phytochemical constituents and haematological activities of the isolated oil in Wistar rat fed with high lipid diet. Powdered leaves of Abrus precatorious were extracted and phytochemical screening was done according to prescribed standard methods, while vacuum liquid chromatography (VLC) was adopted for oil isolation of the crude extract and characterized by gas chromatography-mass spectrometry (GC-MS). Thirty adult Wistar rats were randomly arranged into six groups (A, B, C, D, E and F) and treated under certain conditions. Haematological analyses were performed according to standard procedures. Saponins, alkaloids, terpenoids, flavonoids and glycosides were present. …

Determination Of Sugars, Amino Acids, Ph And Alcohol In Bamboo Beverage From Southern Highlands, Tanzania, Lilian D Kaale

Tanzania Journal of Science

The amounts of sugars and amino acids play significant roles in defining the fermentation process and quantifying the alcohol levels in beverages, while pH affects the biological stability, colour, oxidation rate, and protein stability of alcoholic beverages. This study investigated the sugar content, amino acids, alcohol levels, and pH of bamboo beverage from Tanzania's southern highlands. During storage, the sugars significantly decreased (p < 0.05), especially when kept at room temperature from 52.96 to 0.00 (source 1), 53.35 to 0.00 (source 2) and 53.57 to 0.00 (source 3) g/L for fructose, from 47.93 to 14.78 (source 1), 47.23 to 14.91 (source 2) and 47.61 to 14.77 (source 3) g/L for glucose, and from 0.40 to 0.00 (source 1), 0.36 to 0.00 (source 2) and 0.37 to 0.00 (source 3) g/L for sucrose after six days of storage. A total of 15 amino acids were determined from the bamboo beverage with tyrosine being the most prevalent (597.68 mg/L for source 1, 599.44 mg/L for source 2 and 597.83 mg/L for source 3), followed by valine (261.13 mg/L for source 1, 261.24 mg/L for source 2 and 262.54 mg/L for source 3), threonine (76.69 mg/L for source 1, 76.91 mg/L for source 2 and 77.13 mg/L for source 3), and serine (66.37 mg/L for source 1, 67.23 mg/L for source 2 and 66.68 mg/L for source 3). After six days of storage at room temperature, there was a significant decrease in pH from 4.04 to 3.63. Alcohol content ranged from 3.11 to 9.05% v/v at the room temperature storage. These results might facilitate the optimal use of bamboo beverages, which have been neglected due to lack of scientific information such as amino acid and sugar levels. Keywords:    Bamboo beverage, ulanzi, amino acids, sugars, alcohol content.

Angiogenic Supports For Microvascular Engineering, Zain Siddiqui

Dissertations

Ischemic tissue disease is caused by a lack of circulation / blood supply to tissue. This can be treated by introducing a number of angiogenic (pro-blood vessel forming) factors into the tissue. This work presents strategies for ischemic tissue treatment utilizing a novel proangiogenic self-assembling peptide hydrogel platform. To demonstrate the utility of this platform, its use alone as an angiogenic therapeutic (both alone as a self-assembling hydrogel and with two-component systems), and its ability to vascularize implants is explored. Due to these angiogenic scaffolds demonstrating efficacy to regenerate microvasculature, this work evaluates diseases that can be treated by the …

Production Of Biofuel Using Magnetic Nanocatalyst Zno-Ni0.5zn0.5fe2o4-Fe2o3: A Mini-Review Of Recent Studies, Nida Ziafat Miss, Majid Mahmood

Journal of Bioresource Management

As conventional fossil fuels are becoming limited, it is critical to find alternative clean and renewable energy sources. Biodiesel is a degradable and renewable form of fuel made up of long-chain fatty acid esters that can be generated from either plants or animals. It is a mixture of long-chain alkyl esters made through a transesterification reaction with alcohol and catalyst. Due to the high cost of petroleum, the concept of biofuel production as an alternative source has increased in recent years. The present mini-review summarizes some recent studies on alternative methods for the production of biofuel. The review concludes that …

Feasibility And Effectiveness Of A Worksite-Weight-Loss Program For Cancer Prevention Among School-District Employees With Overweight And Obesity, Che Young Lee, Michael C Robertson, Hannah Johnston, Thuan Le, Margaret Raber, Ruth Rechis, Katherine Oestman, Alise Neff, Amber Macneish, Karen M Basen-Engquist

Faculty, Staff and Students Publications

The effects of Vibrant Lives, a 6-month worksite-weight-loss program, were examined in a cohort of school-district employees with overweight or obesity. The VL Basic (VLB) participants received materials and tailored text messages, the VL Plus (VLP) participants additionally received WIFI-enabled activity monitors and scales and participated in health challenges throughout the school year, and the VL Plus with Support (VLP + S) participants additionally received coaching support. The levels of program satisfaction and retention and changes in weight, physical activity (PA), and diet were compared across groups using Pearson chi-square tests, repeated-measure mixed models, and logistic regression. After the program, …

Apoptotic Effect Of Bortezomib On Pancreatic Islet Cells In Stz-Induced Diabetic Rats, Çiğdem Ekin, Neslihan Tekin Karacaer, Mehtap Tarhan Karaoğlan, Ibrahim Örün, Kamile Öztürk

Makara Journal of Health Research

Background: This study aimed to investigate the possible apoptotic role of bortezomib (BMZ) on pancreatic islets of streptozotocin (STZ)-induced diabetic rats.

Methods: Sprague-Dawley rats were divided into groups that were administered BMZ alone or in combination with STZ. To evaluate the effect of BMZ on the development of diabetes, blood glucose levels were measured regularly in the animals. Islet cell viability was determined by staining the islets with fluorescein diacetate and propidium iodide. Expression of the Bcl-2 and bax genes was determined in islet cells by quantitative real-time polymerase chain reaction.

Results: Administering STZ-induced hyperglycemia in the …

Hiv-Tat Exacerbates The Actions Of Atazanavir, Efavirenz, And Ritonavir On Cardiac Ryanodine Receptor (Ryr2), Imam Abdulrahman Bin Faisal University, Chengju Tian, Sean R. Bidasee, Zachary L. Venn, Evan Schroder, Nick Y. Palermo, Mohammad Alshabeeb, Benson J. Edagwa, Jason J. Payne, Keshoer R. Bidasee

Department of Biochemistry: Faculty Publications

The incidence of sudden cardiac death (SCD) in people living with HIV infection (PLWH), especially those with inadequate viral suppression, is high and the reasons for this remain incompletely characterized. The timely opening and closing of type 2 ryanodine receptor (RyR2) is critical for ensuring rhythmic cardiac contraction–relaxation cycles, and the disruption of these processes can elicit Ca²⁺ waves, ventricular arrhythmias, and SCD. Herein, we show that the HIV protein Tat (HIVTat: 0–52 ng/mL) and therapeutic levels of the antiretroviral drugs atazanavir (ATV: 0–25,344 ng/mL), efavirenz (EFV: 0–11,376 ng/mL), and ritonavir (RTV: 0–25,956 ng/mL) bind to and modulate the …

Therapies For Mitochondrial Disorders, Kayli Sousa Smyth, Anne Mulvihill

SURE Journal: Science Undergraduate Research Experience Journal

Mitochondria are cytoplasmic, double-membrane organelles that synthesise adenosine triphosphate (ATP). Mitochondria contain their own genome, mitochondrial DNA (mtDNA), which is maternally inherited from the oocyte. Mitochondrial proteins are encoded by either nuclear DNA (nDNA) or mtDNA, and both code for proteins forming the mitochondrial oxidative phosphorylation (OXPHOS) complexes of the respiratory chain. These complexes form a chain that allows the passage of electrons down the electron transport chain (ETC) through a proton motive force, creating ATP from adenosine diphosphate (ADP). This study aims to explore current and prospective therapies for mitochondrial disorders (MTDS). MTDS are clinical syndromes coupled with abnormalities …

Impact Of Covid-19 On A Worksite Weight Loss Program For Employees With Overweight And Obesity, Che Young Lee, Michael C Robertson, Kendahl Servino, Thuan Le, Margaret Raber, Katherine Oestman, Karen M Basen-Engquist

Faculty, Staff and Students Publications

OBJECTIVE: The COVID-19 pandemic has been shown to be negatively associated with physical activity engagement, adherence to healthy diet, and weight management among people with obesity. The current study examined COVID-19-related changes in weight, physical activity (PA), and diet among employees with obesity or overweight who participated in Vibrant Lives (VL), a worksite weight loss program.

METHODS: School district employees participated in the 6-month VL weight loss program and were categorized into non-COVID-era participants and COVID-era participants. Participants completed questionnaires about PA and dietary intake at baseline and follow-up. COVID-era participants reported the effects of pandemic on their behaviors. Changes …

Machine Learning And Protein Allostery, Sian Xiao, Gennady M. Verkhivker, Peng Tao

Mathematics, Physics, and Computer Science Faculty Articles and Research

The fundamental biological importance and complexity of allosterically regulated proteins stem from their central role in signal transduction and cellular processes. Recently, machine-learning approaches have been developed and actively deployed to facilitate theoretical and experimental studies of protein dynamics and allosteric mechanisms. In this review, we survey recent developments in applications of machine-learning methods for studies of allosteric mechanisms, prediction of allosteric effects and allostery-related physicochemical properties, and allosteric protein engineering. We also review the applications of machine-learning strategies for characterization of allosteric mechanisms and drug design targeting SARS-CoV-2. Continuous development and task-specific adaptation of machine-learning methods for protein allosteric …

Systemic Delivery Of Divalent Europium From Ligand Screening With Implications To Direct Imaging Of Hypoxia, Md Mamunur Rashid, Brooke A Corbin, Pavan Jella, Caitlyn J Ortiz, Md Abul Hassan Samee, Robia G Pautler, Matthew J Allen

Faculty, Staff and Students Publications

Hypoxia is a hallmark of many diseases, including cancer, arthritis, heart and kidney diseases, and diabetes, and it is often associated with disease aggressiveness and poor prognosis. Consequently, there is a critical need for imaging hypoxia in a noninvasive and direct way to diagnose, stage, and monitor the treatment and development of new therapies for these diseases. Eu-containing contrast agents for magnetic resonance imaging have demonstrated potential for in vivo imaging of hypoxia via changes in metal oxidation state from +2 to +3, but rapid oxidation in blood limits EuII-containing complexes to only studies compatible with direct injection to sites. …

Surveillance Of Antimicrobial Resistance In Veterinary Medicine In The United States: Current Efforts, Challenges, And Opportunities, Juliana M. Ruzante, Beth Harris, Paul Plummer, Raissa R. Raineri, John Dustin Loy, Megan Jacob, Orhan Sahin, Amanda J. Kreuder

School of Veterinary and Biomedical Sciences: Faculty Publications

Antimicrobial resistance (AMR) is a global problem facing human, animal, plant, and environmental health by threatening our ability to effectively treat bacterial infections with antimicrobials. In the United States, robust surveillance efforts exist to collect, analyze, and disseminate AMR data in human health care settings. These tools enable the development of effective infection control methods, the detection of trends, and provide the evidence needed to guide stewardship efforts to reduce the potential for emergence and further spread of AMR. However, in veterinary medicine, there are currently no known equivalent tools. This paper reviews efforts to reduce the potential for emergence …

Compatibility Of Crude Oil Blends─Processing Issues Related To Asphaltene Precipitation, Methods Of Instability Prediction─A Review, Krzysztof Bambinek, Andrzej Przyjazny, Grzegorz Boczkaj

Natural Sciences Publications

Processing crude oil of variable composition, especially due to the need to process crude oil blends obtained from various sources, presents a tremendous process challenge. This is mainly due to the destabilization of the colloidal system manifested mostly by the precipitation of the asphaltene fraction. The precipitation of asphaltenes from crude oil is a serious problem during extraction, transport, and processing. In the latter case, engineers and scientists have spent a lot of time determining what mechanisms are conducive to the occurrence of this phenomenon. On the one hand, there was a scientific curiosity about the principles of the nanoworld …

Arginine Methylation Of The Pgc-1Α C‑Terminus Is Temperature- Dependent, Meryl Mendoz, Mariel Mendoza, Tiffany Lubrino, Sidney Briski, Immaculeta Osuji, Janielle Cuala, Brendan Ly, Ivan Ocegueda, Harvey Peralta, Benjamin A. Garcia, Cecilia Zurita-Lopez

Biology, Chemistry, and Environmental Sciences Faculty Articles and Research

We set out to determine whether the C-terminus (amino acids 481–798) of peroxisome proliferator-activated receptor gamma coactivator-1 alpha (PGC-1α, UniProt Q9UBK2), a regulatory metabolic protein involved in mitochondrial biogenesis, and respiration, is an arginine methyltransferase substrate. Arginine methylation by protein arginine methyltransferases (PRMTs) alters protein function and thus contributes to various cellular processes. In addition to confirming methylation of the C-terminus by PRMT1 as described in the literature, we have identified methylation by another member of the PRMT family, PRMT7. We performed in vitro methylation reactions using recombinant mammalian PRMT7 and PRMT1 at 37, 30, 21, 18, and 4 °C. …

Dissecting Interactions Across Gene Regulatory Layers In C. Elegans, Morgan Taylor

Biological Sciences Theses and Dissertations

The nematode Caenorhabditis elegans is a powerful tool for studying nervous system genetics. Though relatively simple compared to mammals, C. elegans boasts a remarkably well-conserved neuronal genome and proteome, and its utility in the characterization of neuronal genes has been well-established. However, gene expression is often controlled by complex interactions between multiple genes, and teasing apart the functions of individual genes within such networks remains a challenge. Dissecting these interaction networks is crucial in determining the multifaceted functions of important, conserved regulatory genes. Here we explore interactions between gene regulatory layers in the C. elegans nervous system, employing a synthetic …

Quantum Computations And Molecular Dynamics Simulations: From The Fundamentals Of Antimicrobial Resistance To Neurological Diseases, Angel Tamez

Electronic Theses and Dissertations

Biophysical phenomena are modeled using a combination of quantum and classical methods to interpret and supplement three distinct and diverse problems in this dissertation. In the first project, decarboxylation reactions are ubiquitous across chemical and biological disciplines, yet the origin of non-catalytic solvent effects remains elusive. Specific solvent structure and energetics have not been well described for the monoanion of malonate, nor corrected from the gas-phase charge-assisted intramolecular hydrogen bond model known as “pseudochair”. In the aqueous phase, a low-lying energy conformer known as the “orthogonal conformation” is computed to be preferred by a three-water cluster of hydrogen bonding over …

Dynamics Of Nucleosome Assembly Characterized By Atomic Force Microscopy, Tommy Stormberg

Theses & Dissertations

Nucleosomes are the basic repeating unit defining the assembly and function of chromatin. Understanding the fundamental mechanisms of nucleosome structure and dynamics is critical to elucidating the chromatin assembly process. This dissertation describes my work in elucidating the role of different factors that drive the nucleosome dynamics.

In my first study, we characterized, for the first time, the effect of sequence on nucleosome assembly. We then characterized the role of internucleosomal interactions, discovering a critical role internucleosomal interactions in the assembly of higher order structures.

Based on the previous study and literature regarding histone tails, we hypothesized the histone H4 …

Characterization Of Ape1 And Dna G-Quadruplex Interaction In Transcription Regulation And Dna Damage Repair, Suravi Pramanik

Theses & Dissertations

Human AP Endonuclease 1 (APE1) is the primary enzyme in the base excision repair (BER) pathway that repairs apurinic/apyrimidinic (AP) sites, the most frequently formed DNA lesions in the genome. Recently, through genome-wide mapping analysis, we have shown that APE1, as well as its post-translationally modified form, acetylated APE1 (AcAPE1), is enriched in the gene regulatory regions. The APE1/AcAPE1-enriched regions also harbor Guanine (G)-rich sequences that fold into DNA secondary structures called G-quadruplexes (G4s). Our lab has demonstrated a strong genome-wide correlation between the occurrence of G4 structures and the binding of APE1 and AcAPE1. However, it is unknown whether …

Structural And Inhibitory Studies On (I)Two Mycobacterium Tuberculosis Enzymes Essential For Capsular Glucan Biosynthesis And Mrna Degradation: (Ii) Hantann Virus L-Protein Endonuclease Domain, Hettiarachchige Thilina D. Jayasinghe

Theses & Dissertations

Mycobacterium tuberculosis (Mtb) is the pathogenic bacterium species that causes Tuberculosis (TB). Understanding the major biosynthetic pathways responsible for cell viability is essential in developing new drugs against Mtb. The first two projects will reflect our approach in identifying inhibitors against Mtb GlgE, Mtb GpsI, and characterization of protein inhibitor interactions using X-ray crystallography.

The enzyme GlgE plays an essential role in the α-glucan biosynthesis pathway in Mtb cells. These α-glucans are one of the major structural units in the Mtb capsule. GlgE catalyzes the elongation of α-glucan by transferring maltose from maltose-1-phosphate (M1P) to the non-reducing end …

Structural And Biochemical Studies Of Three Enzymes Involved In Amino Acid Metabolism To Develop Novel Drugs, Yahani Pankaja Jayasinghe Arachchige

Theses & Dissertations

Intrinsic drug resistance in bacteria predates the clinical use of antibiotics. Additionally, heterogeneous metabolic states and the ability of many bacteria to form biofilms further enhances bacterial survival during infection and exacerbates treatment challenges. This necessitates the identification of novel drugs against new drug targets. These studies focus on the development of compounds targeting enzymes in Mycobacterium tuberculosis (Mtb) and Staphylococcus aureus that avoid intrinsic antibiotic defenses. The Mtb-encoded homoserine transacetylase enzyme (HTA) catalyzes the first step of the methionine biosynthesis pathway that produces methionine and S-adenosyl methionine. These compounds are shown to be essential for both dormant …

The Role Of Parkin In Mitochondrial Dna, Eliezer Lichter

Theses & Dissertations

Mitochondria are at the center of biological phenomena such as aging and diseases, especially neurodegenerative diseases. While the discovery of mitochondria only came approximately 200 years after the cell was discovered, a lot of progress has been made since. The mitochondrial genome encodes proteins vital for mitochondrial function. These proteins are only a subset of the proteins present in mitochondria; the rest are nuclear encoded. The nucleus also encodes cytosolic proteins vital for mitochondrial maintenance. One of these is Parkin, an E3 ubiquitin ligase that ubiquitinates mitochondrial proteins as mitochondria become depolarized. Its activity has been shown to be involved …

Role Of E3 Ubiquitin Ligase Ubr5 In B Cell Development And Mantle Cell Lymphoma, Tyler J. Gilbreath

Theses & Dissertations

UBR5 is part of the ubiquitin proteasome system (UPS), most well-known as a degradation and recycling pathway in which proteins are tagged with a chain of ubiquitin protein and degraded by the proteasome. However, the UPS is multifunctional and other important roles include tagging protein with ubiquitin for cell signaling purposes. UBR5 is a homologous to the E6AP C-terminus (HECT) E3 ubiquitin ligase, meaning ubiquitin is transferred to UBR5 on a cysteine residue within the HECT domain and then onto a target substrate. UBR5 has mutations in many types of cancers: breast, ovarian, liver, and lymphomas. Recently published data shows …