Cell Biology Commons^™

Oxidative Stress Mediated Glutamate Release And Nmda Receptor-Dependent Synaptic Remodeling In Radiation-Induced Cognitive Dysfunction, Thanh Lam

Dissertations and Theses (Open Access)

In children younger than 14 years old, the brain and other parts of the central nervous system are the most common sites for solid tumors. Radiotherapy is an effective treatment for central nervous system (CNS) tumors. However, it often causes a progressive decline in cognitive functions, which is especially devastating for pediatric patients. Although post-mitotic neurons are generally considered resistant to radiation-induced immediate cell death, ionizing radiation causes complex neurochemical and structural changes that damage synaptic integrity. In this study, we examined the molecular cascades following a 10 Gy radiation dose applied to mouse cortical neurons. We found that radiation-induced …

In Vitro Reversal Of Abc Transporter Mediated Multidrug Resistance In Human Ovarian And Non-Small Cell Lung Cancer Models, Alison K. Kellom, Pia D. Vogel

Biological Sciences Theses and Dissertations

One of the major causes of treatment failure in aggressive cancers is multidrug resistance (MDR), which is linked to the overexpression of membrane efflux proteins that export chemotherapeutics from cancer cells. This mechanism prevents chemotherapeutic drugs from reaching cytotoxic concentrations intracellularly, allowing the cancer to survive. Two primary mediators of this mechanism are P-glycoprotein (P-gp) and Breast Cancer Resistance Protein (BCRP). P-gp and BCRP are transmembrane ATP-binding cassette (ABC) transporters that are frequently overexpressed in MDR cancers. They utilize the binding and hydrolysis of ATP to transport a diverse range of amphipathic molecules of varying size (Schinkel and Jonker, 2003), …

Cell Cycle Inhibition: Illudin S And Its Effects On Cdk2 In Ewing Sarcoma, Stephanie Diez, Natalie Flores, Alexandria Hernandez, Viviana Palacios, Terry Jo Shackleford

Cell and Molecular Methods

Ewing Sarcomas are aggressive round cell mesenchymal neoplasmas that have a high occurrence in children and young adults. CDK2 is a protein that is involved in the G1 phase of the cell cycle, which promotes the transition to the S phase. CDK2 kinase activation is mainly observed in the G1/S-phase transition.3 CDK2 binds to Cyclin proteins is responsible for entry and progression, thereby leading to maximal apoptosis activity in the S-phase. Illudin S is a drug that has been known to target cancer-specific cells, such as leukemia. Illudin S, in general are a cytotoxic metabolite that comes from plants, specifically …

Yap1 Knockdown And Panobinostat Treatment Increase Apoptotic Response And Decrease Gene Expression In Ewing Sarcoma Cells, Luna Collazo-Garcia, Alejandra Favela Santos, Madeline Torres-Salazar, Isabella Toscano, Terry Jo Shackleford

Cell and Molecular Methods

Ewing sarcoma (EWS) is considered to be one of the most aggressive pediatric malignancies, often characterized by its dysregulated gene expression driven by oncogenic fusion proteins. The Hippo signaling effector Yes-associated protein 1 (YAP1) has been known in promoting cell proliferation, survival, and therapeutic resistance in multiple cancers. However, its role in Ewing sarcoma response to treatment remains unclear. This study investigated whether YAP1 knockdown enhances the sensitivity of Ewing sarcoma cells to the histone deacetylase inhibitor Panobinostat. Ewing sarcoma, ES8, cells were transfected with a YAP1-targeting siRNA (siYAP1) or a non-targeting control (siControl) and treated with DMSO, 0.1 μM, …

Everolimus Treatment Combined With Akt1 Knockdown Increased Apoptosis And Decreased Cell Proliferation In Ewing Sarcoma Cells, Arisha Arif, Alfie Barcenez, Sophia Ruter, Nicole Vanegas-Riddick, Terry Jo Shackleford

Cell and Molecular Methods

The purpose of this study is to use the gene AKT1, due to the interest in AKT1’s role in cancer cell proliferation, and the drug Everolimus, to determine if combined targeted therapy works as a more efficient therapeutic approach. Ewing Sarcoma has been connected to chromosomal translocations and is most common in pediatric patients. It is most often treated with chemotherapy and local treatments. It may be connected to the gene AKT1 due to how it regulates cell metabolism, growth, and proliferation. The gene mTOR is similarly connected to cell metabolism and proliferation, and is inhibited by the drug Everolimus. …

Sirna Knockdown Of Rptor Reduces Rptor Expression, Increases Brd4 Expression, And Alters Proliferation And Apoptosis In Ewing's Sarcoma Cells, Sergio Cipriano, David Leavitt, Michael Olivia, Liam Valdez, Terry Jo Shackleford

Cell and Molecular Methods

Ewing sarcoma is a highly aggressive cancer that primarily affects children and young adults. Although treatment options exist, many patients do not respond effectively, showing the need for improved targeted therapies. RPTOR is a key in mTORC1 complex which regulates cell growth, proliferation, and survival. LY2874455 is a selective pan-FGFR inhibitor that targets growth factor signaling pathways involved in tumor progression, and FGFR signaling interacts with pathways such as mTOR, making it a potential target for combination therapies. We hypothesized that silencing RPTOR in Ewing sarcoma cells would disrupt mTOR signaling and alter expression of genes linked to cell survival …

Everolimus And Sirna-Mediated Mtor Inhibition Reduces Proliferation And Promotes Apoptosis In Ewing Sarcoma Cells, Dylan Calvert, Malorie Martinez, Alexa Miner, Ellis Quiroga, Terry Jo Shackleford

Cell and Molecular Methods

Ewing Sarcoma (ES) is an aggressive pediatric bone cancer characterized by rapid cell proliferation and poor prognosis, making the identification of therapeutic targets critical. One of  the mechanistic targets is rapamycin (mTOR) signaling pathway, which is critical for regulating cell growth, proliferation, and survival. Abnormal activation of the mTOR signaling pathway has been linked to the progression of ES, as it drives uncontrolled cell growth and apoptosis resistance. Because mTOR represents a promising therapeutic target for ES treatment, we hypothesized that inhibiting mTOR activity through an siRNA-mediated knockdown or through Everolimus drug treatment, would reduce cell proliferation and promote ES …

Analysis Of The Effects Of Astaxanthin On Human Colorectal Cancer Cells, Kara A. Walters

Theses/Capstones/Creative Projects

Astaxanthin (AXT) is an antioxidant carotenoid that is produced by the microalgae Haemococcus pluvialis. This supplement is best known for its potential health benefits including anti-inflammatory, antitumor, immunomodulatory, anticancer and antidiabetic activities. Astaxanthin is marketed as an oral dietary supplement and is widely used in the nutraceutical industry as well as a coloring agent in the food industry. Since Astaxanthin has been increasingly popular as a dietary supplement, cytotoxicity is relevant to consumer exposure. Obtaining the IC50, the concentration that inhibits 50% of cell growth, is important to find how Astaxanthin may interact with cancer, and this can be found …

Genetic Screen For Regulators Of Pol4, A Dna Repair Polymerase In Saccharomyces Cerevisiae, Pasang Dolma Sherpa

Theses and Dissertations

In Saccharomyces cerevisiae, DNA polymerase 4 (POL4) is the beta repair polymerase, the product of the POL4 gene, and is involved in base excision repair (BER) and microhomology-mediated end joining (MMEJ). Despite its involvement in these repair pathways and its conservation across eukaryotes, deletion of POL4 shows no detectable phenotype under standard laboratory conditions. I hypothesized that unknown genes act as backup systems, providing redundant activities that allow pol4Δ cells to survive. To test this, a genetic screen for mutants showing synthetic lethality with pol4Δ was implemented. I constructed a strain lacking the POL4 gene and carrying …

Inosine Accelerates Cancer Cell Killing By The Experimental Antifolate Ucp1162: Implications For Novel Combination Treatments, Reshma Ramesh, Charles Giardina, Alan Kuo

Honors Scholar Theses

Antifolates disrupt one-carbon metabolism (OCM), which stops nucleotide synthesis and therefore slows down cell proliferation. Our experimental antifolate, UCP1162, stops de novo purine synthesis and thymidine synthesis by targeting the OCM pathway. We investigated whether the downstream metabolites of OCM pathway: methionine, thymidine, and inosine, affect the cell death caused by UCP1162 using MV4-11 leukemia cells. Thymidine was found to partially rescue MV4-11 cells from UCP1162, in contrast, inosine was found to accelerate the cell death caused by UCP1162. These cytotoxic effects of UCP1162 alone and in combination with inosine were irreversible, as removal of treatment did not restore cell …

Effects Of M6a Dna Methylation By Bacterial Methyltransferase In Colorectal Cancer, Fabian Alejandro Mendoza Galvan

Dissertations and Theses (Open Access)

Effects of m6A DNA methylation by bacterial methyltransferase in colorectal cancer Fabian Alejandro Mendoza Galvan Advisory Professor: Angela H. Ting, Ph.D. Fusobacterium nucleatum animalis (Fna) is found in the human oral cavity and gut. A distinct clade of Fna is primarily enriched in the tumor microenvironment (TME) and within colorectal cancer (CRC) cells. This clade DNA methylation pattern is primarily catalyzed by a cell-cycle regulated methyltransferase (CcrM) ortholog, M.FnI, that targets the GANTC sequence motif through methyl-6-Adenine (m6A) DNA methylation. We hypothesized that M.FnI enzyme can induce m6A methylation abnormalities in CRC cells to promote cancer progression. Evidence for endogenous …

From Antigen Presentation To Tumor Control: Mechanisms Of Type I Conventional Dendritic Cell-Based Cancer Vaccines, Josue E. Pineda

Dissertations and Theses (Open Access)

Type 1 conventional dendritic cells (cDC1s) are important for generating and sustaining antitumor immunity. Accordingly, the abundance of cDC1s in human tumors correlates with improved outcomes in cancer. Capitalizing on this role, we previously demonstrated that vaccination with in vitro-derived murine cDC1s elicits durable tumor control in multiple preclinical models; however, the immunological mechanisms underlying the efficacy of cDC1 vaccination remain unclear. Here, we examined whether in vitro-derived cDC1s resemble tumor-infiltrating DC populations and whether MHC-I and MHC-II antigen presentation contribute to cDC1-mediated tumor control following vaccination in melanoma.

As expected, MHC-I- or MHC-II-deficiency had minimal impact on …

Targeting Rna Polymerase I In Ewing Sarcoma Treatment, Alexis Bruce

Theses

Ewing sarcoma is a rare and aggressive pediatric bone cancer with poor survival rates in patients, as low as 30% in advanced or recurrent cases. There are limited treatment options, making molecularly targeted therapy vital to explore. Through CRISPR scans of Ewing sarcoma cell lines, ribosome biogenesis was highlighted as a potential target. As RNA polymerase I is a key component of ribosome biogenesis, the cytotoxic ability of two RNA Polymerase I inhibitors, CX-5461 and BMH-21, were used on patient-derived Ewing sarcoma cells. The efficacy of the drugs on two cell lines was determined via measuring cell viability, migration potential, …

Cellular And Molecular Characterization Of Ube3a Function In Cic-Dux4 Sarcoma, Jesse D. Walker

Theses

CIC-DUX4 sarcoma (CDS) is a rare and extremely aggressive soft tissue sarcoma that primarily affects children and young adults. CDS is characterized by an oncogenic chromosomal translocation. Current treatments for CDS are similar to those in other sarcomas like surgery, chemotherapy, and radiation. Treatments, however show that CDS responds poorly compared to other sarcomas, due to relapses of localized disease at high rates and short duration response of treatment, proving the importance of understanding CIC-DUX4’s complex role on how it regulates overall gene expression in CDS cells from a molecular approach.

UBE3A is a ubiquitin protein ligase that plays a …

Differential Effects Of Veratridine And 5-Fluorouracil On Ubxn2a-Targeted Mortalin And Rictor Proteins In Patient-Derived Colorectal Cancer Cells, Kate S. Schraufnagel

Honors Thesis

Colorectal cancer (CRC) is a leading cause of cancer-related mortality, particularly in patients with metastatic CRC and/or those who have developed resistance to conventional chemotherapy. There has been a significant rise in early-onset CRC (EOCRC) incidences in patients under age 50. Due to lack of screening, these patients are commonly diagnosed in the later stages where there is a lack of effective therapies. This highlights the need for targeted therapies that address the molecular drivers of tumor progression and treatment resistance. UBXN2A is a tumor suppressor protein that regulates key oncogenic pathways in CRC, including Mortalin-2 (mot-2)-mediated p53 suppression and …

Stat-Independent Functions Of Janus Kinases 1 And 2 Are Obligatory For The Postnatal Development Of Mammary Epithelial Ducts, Rayane Dennaoui, Madison N. Wicker, Carson Moen, Michaela Schlederer, Kerry Vistisen, Aleata A. Triplett, Thomas Rülicke, Hallgeir Rui, Lukas Kenner, Emilio Casanova, Kay-Uwe Wagner

Department of Pharmacology, Physiology, and Cancer Biology Faculty Papers

Janus kinases 1 and 2 and STAT transcription factors are critical signaling nodes for numerous growth factors. In the mammary gland, JAK2 and STAT5a/b are essential for alveolar cell differentiation and lactation, but little is known about the cooperative roles of JAKs and STATs before pregnancy. We examined female mice conditionally deficient in JAK1/2 and discovered that both kinases jointly regulate epithelial cell proliferation and ductal morphogenesis. To assess the role of downstream STATs, we generated genetic models co-deficient in STAT3/5a/5b with or without STAT1 or JAK1. Although loss of STAT3/5a/5b leads to a JAK1-dependent upregulation of STAT1, the formation …

Exploring The Synergistic Effects Of Cisplatin And Curcumin In Osteosarcoma Cells, Ellis Stafford, Alexa Cabral, Andrea Florian Ph.D., Reese Nagy

SPARK Symposium Presentations

Osteosarcoma (OS) is a highly aggressive bone cancer characterized by rapid metastasis, which drastically reduces patient survival rates from 70% in localized cases to 30% upon metastasis. Current treatments combining chemotherapy with cisplatin and surgical intervention are often ineffective against metastatic OS and are associated with significant side effects. Cisplatin targets cancer cells by binding to DNA, disrupting transcription and replication, and inducing apoptosis. To address the challenges associated with current treatments, this study investigates the potential of combining cisplatin with curcumin, the bioactive compound derived from turmeric, as a novel therapeutic approach. Curcumin has shown anticancer properties by inducing …

Investigation Of Genx Exposure To Pathways Associated With Colorectal Cancer Risk, Emily J. Ferguson

Theses and Dissertations--Toxicology and Cancer Biology

Per- and polyfluoroalkyl substances (PFAS) are persistent environmental contaminants widely detected in drinking water and food sources, resulting in chronic human exposure. Among these compounds, hexafluoropropylene oxide dimer acid (HFPO-DA), commonly known as GenX, has been introduced as a short-chain replacement for legacy PFAS such as perfluorooctanesulfonic acid (PFOS) and perfluorooctanoic acid (PFOA). Although GenX is believed to be a safer alternative, emerging research suggests it can still affect human health.

Colorectal cancer (CRC) is the third most commonly diagnosed cancer and the second leading cause of cancer-related death in the United States, highlighting the need to better understand environmental …

Uncovering The Mechanism Of Reep2-Mediated Emt-Driven Membrane Trafficking In Lung Adenocarcinoma, Kevin Fulp

Theses and Dissertations--Toxicology and Cancer Biology

Membrane trafficking is frequently disrupted during cancer progression, and the underlying mechanisms remain largely unknown. Currently, no effective drugs target dysregulated membrane trafficking for cancer treatment. Recent evidence has demonstrated that epithelial-to-mesenchymal transition (EMT) in lung adenocarcinoma (LUAD) employs a membrane trafficking program to coordinate cancer cell invasion and immunosuppression. To further dissect the pro-tumorigenic membrane trafficking program, we initiated an in vivo CRISPRi screen to assess more than 2,000 membrane trafficking-related genes in a syngeneic mouse LUAD model. We identified REEP2, an endoplasmic reticulum (ER) shaping protein, as a novel regulator of EMT-driven membrane trafficking. High REEP2 expression is …

Reep2-Driven Pro-Metastatic Secretion Promotes Lung Cancer Progression, Oluwafunminiyi E. Obaleye

Theses and Dissertations--Toxicology and Cancer Biology

Membrane trafficking plays a critical role in cellular function and is frequently dysregulated in cancer to promote metastasis. In lung adenocarcinoma (LUAD), the epithelial-to-mesenchymal transition (EMT) activating transcription factor, ZEB1, drives a pro-metastatic membrane trafficking program; however, the underlying molecular mechanisms remain poorly understood. Using a CRISPR interference (CRISPRi) in vivo screen of 2,099 membrane trafficking regulators in a syngeneic mouse model of EMT-driven LUAD, we identified REEP2 — an endoplasmic reticulum (ER) shaping protein — as a critical regulator of tumor progression. REEP2 mRNA expression correlates with poor prognosis, EMT signatures, and an immunosuppressive tumor microenvironment in LUAD patients. …

Determining Genes Involved In Recovery From Chemotherapy In 4t1, Emt6, And Eo771 Breast Cancer Cells, Akash Jagdeesh, Joseph Landry Ph.D.

Undergraduate Research Posters

Breast cancer is one of the most common types of cancer, and often has poor prognosis. Traditional treatments for breast cancer include chemotherapy, which involves a chemical attack on all growing cells within the body. However, these treatments are not 100% effective, and patients might experience recurrence in their cancer months or years after achieving remission. Cancer cells can evade chemotherapy through five mechanisms: senescence, quiescence, cytoprotective autophagy, and apoptosis/necroptosis suppression. Prior studies have conducted CRISPR screens and experiments involving inhibition of epigenetic regulators, to alter the regulation of genes that can contribute to breast cancer chemotherapy resistance. This study …

Ex Vivo Sensitivity Assays With Molecular Validation To Guide Preclinical Drug Selection For Schwann Cell Tumors, Ethan W. Hass

Graduate Studies Theses and Dissertations 2026

Schwann cells are the glial cell of the peripheral nervous system. They are dependent on receptor tyrosine kinase-mediated RAS signaling, cell matrix adhesion, and cell-cell contact to proliferate during nerve development and repair. These pathways become deregulated with loss of function of the merlin tumor suppressor encoded by NF2, leading to benign tumors called schwannomas. Patients with NF2-related schwannomatosis (NF2-SWN) develop bilateral vestibular schwannomas that cause hearing loss, tinnitus, and death from brainstem compression if untreated. Severe NF2-SWN causes multiple spinal and peripheral schwannomas and neuropathic pain. Schwannomas require careful monitoring, trial and error use of repurposed anti-cancer …

Evaluating The Sna1 Gene Using Crispr Mediated Knockdown In Ewing Sarcoma Cells, Rosanna Jees, Sonia Cerrillo, Terry Jo Shackleford

Mechanisms of Disease

Ewing sarcoma is a pediatric cancer with limited therapeutic options and poor long-term survival. CRISPR–Cas9–mediated gene editing provides a powerful tool for investigating tumor molecular behavior and identifying potential therapeutic targets. In this study, we worked with CRISPR–Cas9 in Ewing sarcoma ES8 cells to evaluate the roles of the transcription factors SNAI1 and SNAI2, both implicated in epithelial–mesenchymal transition and cancer progression. Using guide RNAs targeting each gene, we assessed proliferation, apoptosis, migration, and long-term survival through Incucyte live-cell imaging and colony-formation assays. Knockout of SNAI1 resulted in decreased cell proliferation and reduced migratory capacity compared with controls, suggesting a …

Δ-Valerobetaine As A Novel Inhibitor Of Breast Cancer Cell Migration: Hinders Cellular Migration Of Mcf-7 Cells Through Reducing Atp Concentrations And Fak Activation, Braxton Ivie, Lincoln Brown, Bryson Lovorn

Student Scholar Symposium

δ-valerobetaine as a Novel Inhibitor of Breast Cancer Cell Migration: Hinders Cellular Migration of MCF-7 Cells Through Reducing ATP Concentrations and FAK Activation

Lincoln Brown, Braxton Ivie, Bryson Lovorn, Joshua Owens

Based on female breast cancer diagnoses from 2014-2020, the CDC reports that the 5-year relative survival rate for local and regional breast cancers was 98.9% and 86.3%, respectively, while the survival rate for metastasized cancers was reportedly 32.4%. These discrepancies in survival highlight an increased mortality rate when cancer metastasizes. Interestingly, aggressive tumors have been shown to metabolize fats at higher rates than low-metastatic tumors. Recently, our group has …

A Molecular Mechanism Of Epithelial To Mesenchymal Transition (Emt): An Evidence Based Lesson Applying Molecular Biology Through The Lens Of Cancer, Sophie Hasson, Melissa Rowland-Goldsmith

Open Educational Resources

This lesson aims to strengthen students’ critical thinking and molecular biology data analysis skills as well as their understanding of concepts related to the hallmark of cancer: tissue invasion and metastasis. Students begin by learning about the invasion of cancer cells, Epithelial-Mesenchymal Transition (EMT), and an important protein involved in EMT: E-cadherin. They then apply molecular biology knowledge to analyze data from multiple papers to infer the relationship between Snail and E-cadherin in different types of cancers. Next, they continue to interpret data from many papers to determine that a repressor transcription factor is present during EMT in cancer cells …

Mitochondria-Mediated Epigenetic Transfer Between Chondrosarcoma And Wild-Type Cells, Caleb C. J. Wyckoff

Biomedical Sciences Theses & Dissertations

Glioblastoma (GB), acute myeloid leukemia (AML), chronic lymphocytic leukemia (CLL), cholangiocarcinoma, and chondrosarcoma (CS) cancers all contain mutations in the gene isocitrate dehydrogenase 2 (IDH2). The mutant IDH2 enzyme exhibits transformation of alpha-ketoglutarate (αKG) into the oncometabolite D-2-hydroxyglutarate (D2HG) in the mitochondria of these cancers. Mitochondrial-mediated transfer between cancer cells and recipient cells is a significant event that impacts the physiology of the receiving cell, specifically the epigenetic landscape. Previous experiments indicating increased DNA methylation in mesenchymal stem cells exposed to IDH1 or IDH2 conditioned medium underscore the potential role of D2HG to alter methylation states. Additionally, the presence of …

Mathematical Model Of Ovarian Cancer Tumor Growth In Mice, Jessica A. Hoffman

Annual Symposium on Biomathematics and Ecology Education and Research

No abstract provided.

Investigating The Role Of Early Growth Response 1 (Egr1) Gene In Riluzole-Induced Apoptosis In Osteosarcoma, Syeda Maryam Azeem

Dissertations, Theses, and Capstone Projects

Osteosarcoma is a rare but aggressive bone malignancy most commonly affecting adolescents and young adults (AYA). With 5-year survival rate stagnating over the last four decades despite the advancements in multi-modal therapy, drug repurposing offers a rapid path to new osteosarcoma treatments. Recent studies suggest that Riluzole, a drug approved for amyotrophic lateral sclerosis (ALS), may be repurposed for osteosarcoma treatment due to its ability to slow tumor progression and induce apoptosis. Previously, we have shown that Riluzole increases reactive oxygen species (ROS), activating c-Abl, which phosphorylates YAP in the nucleus. YAP then forms a complex with p73 to enhance …

Global Erk/Mapk Activation Determines Oncogenic Fitness In Kras-Mutant Pancreatic Ductal Adenocarcinoma, Rachel A. Burge

MUSC Theses and Dissertations

In pancreatic ductal adenocarcinoma (PDAC), ~95% of cases harbor an activating KRAS mutation. The most common KRAS mutations in PDAC are KRAS^G12D (42%), KRAS^G12V (31%), and KRAS^G12R (15%). Patients harboring KRAS^G12R mutations have increased overall survival compared to those with KRAS^G12D/V-mutations. While KRAS^G12D/Vare common in all KRAS-mutant cancers, KRAS^G12Ris only common in PDAC.

KRAS^G12R is unable to activate the lipid kinase PIK3CA, a KRAS effector that is important for tumorigenesis in murine models. To investigate the tumorigenic potential of KRAS^G12R and the mechanisms that enable this mutation …

Impact Of S-Phase Kinase Protien 2 Blockades On Hematopoetic Stem Cell Metabolism, Nicole Elmaraghy

Electronic Theses, Projects, and Dissertations

Hematopoietic stem and progenitor cells (HSPCs) quiescence is vital for the success of bone marrow transplantation, as it preserves long term self- renewal and prevents premature exhaustion (Takubo et al., 2013; Wilson et al., 2008). However, bone marrow transplant (BMT) failure remains a clinical challenge, often due to lack of long-term engraftment and insufficient stress reliance. Both of these characteristics are tightly linked to disrupted stem cell quiescence and metabolic imbalance (Anso et al., 2017; Vannini et al., 2016). One key player is S-phase kinase protein (SKP2), an E3 ubiquitin ligase that targets cell cycle inhibitors, like p27, for proteosome …