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Full-Text Articles in Cell and Developmental Biology

Protein Kinase Ck2 Phosphorylates And Activates P21-Activated Kinase 1, Yong Jae Shin, Yong-Bae Kim, Jeong-Ho Kim Sep 2013

Protein Kinase Ck2 Phosphorylates And Activates P21-Activated Kinase 1, Yong Jae Shin, Yong-Bae Kim, Jeong-Ho Kim

Biochemistry and Molecular Medicine Faculty Publications

Activation of the p21-activated kinase 1 (PAK1) is achieved through a conformational change that converts an inactive PAK1 dimer to an active monomer. In this paper, we show that this change is necessary but not sufficient to activate PAK1 and that it is, rather, required for CK2-dependent PAK1S223 phosphorylation that converts a monomeric PAK1 into a catalytically active form. This phosphorylation appears to be essential for autophosphorylation at specific residues and overall activity of PAK1. A phosphomimetic mutation (S223E) bypasses the requirement for GTPases in PAK1 activation, whereas the constitutive activity of the PAK1 mutant (PAK1H83,86L), postulated to mimic GTPase-induced …


Effects Of Phytochemicals From Rhodiola Crenulata On Highly Invasive Breast Cancer Cell Lines And Embryonic Models Of Migration, Adaris Rodriguez-Cortes Sep 2013

Effects Of Phytochemicals From Rhodiola Crenulata On Highly Invasive Breast Cancer Cell Lines And Embryonic Models Of Migration, Adaris Rodriguez-Cortes

Open Access Dissertations

The root of the Tibetan plant Rhodiola crenulata is part of eastern traditional medicine. Studies have suggested that members of the Rhodiola genus display anticancer properties. In this study we examine the effect of R. crenulata in a cellular model of invasive breast cancer, this disease being the second cause of cancer death among women in the US. Deregulation of the Wnt/β-catenin pathway has been frequently observed in breast cancers and appears to have a key role in the transformation of benign cells to a malignant form. Although mutations of the Wnt growth factor are rarely observed in cancer, the …


Hypothesis Driven Single Nucleotide Polymorphism Search (Hydn-Snp-S), Rebecca J. Swett, Angela Elias, Jeffrey A. Miller, Gregory E. Dyson, G. AndréS Cisneros Sep 2013

Hypothesis Driven Single Nucleotide Polymorphism Search (Hydn-Snp-S), Rebecca J. Swett, Angela Elias, Jeffrey A. Miller, Gregory E. Dyson, G. AndréS Cisneros

Chemistry Faculty Research Publications

The advent of complete-genome genotyping across phenotype cohorts has provided a rich source of information for bioinformaticians. However the search for SNPs from this data is generally performed on a study-by-study case without any specific hypothesis of the location for SNPs that are predictive for the phenotype. We have designed a method whereby very large SNP lists (several gigabytes in size), combining several genotyping studies at once, can be sorted and traced back to their ultimate consequence in protein structure. Given a working hypothesis, researchers are able to easily search whole genome genotyping data for SNPs that link genetic locations …


The Importance Of Epigenetic Phenomena In Regulating Activity Of The Genetic Material, Sin Chan Aug 2013

The Importance Of Epigenetic Phenomena In Regulating Activity Of The Genetic Material, Sin Chan

Senior Honors Projects

Genetics has taught us that genes are represented as discrete sequences within a larger DNA molecule found embedded within the chromosomes of a living cell. Collectively these chromosomes and their associated genes carry all of the instructions for life. Until recently, the prevailing thought has been that genes are destiny in the life of an individual since the genes carry the information that determines the general traits and characteristics associated with that individual. The relatively recent understanding of mechanisms that underlie epigenetic phenomena has led to a rethinking of this concept. Epigenetics describes cellular mechanisms that explain how two individuals …


Metabolic Rescue Of “Glucose Addicted” Cancer Cells In Vitro, Paolo Vignali Mar 2013

Metabolic Rescue Of “Glucose Addicted” Cancer Cells In Vitro, Paolo Vignali

Pursuit - The Journal of Undergraduate Research at The University of Tennessee

Transformations in the glycolytic metabolism of neoplasms modulate their robust cellular division. This characteristic leads to an “addiction” to glucose for continued proliferation and viability. This study investigated whether glucose metabolites could rescue cellular viability in glucose-starvation conditions, a model of the inter-tumoral nutrient-deficient environment. Findings illustrated potential cellular viability rescue with pyruvate addition in glucose-deprived conditions, yet the same potential was not observed with lactic acid, a metabolite that exists at characteristically high concentrations within the intertumoral microenvironment. These results could implicate a predominance of certain metabolic pathways in nutrient-starved cells. Molecular transport capacities across plasma membranes are tied …


Brca1 Dna-Binding Activity Is Stimulated By Bard1, Amanda Simons, Andrew Horwitz, Lea Starita, Karen Griffin, R Williams, J.N. Glover, Jeffrey Parvin Feb 2013

Brca1 Dna-Binding Activity Is Stimulated By Bard1, Amanda Simons, Andrew Horwitz, Lea Starita, Karen Griffin, R Williams, J.N. Glover, Jeffrey Parvin

Amanda Simons

The breast- and ovarian-specific tumor suppressor BRCA1 has been implicated in numerous cellular processes, including transcription, ubiquitination, and DNA repair. Its tumor suppression activity is tightly linked to that of BARD1, a protein that heterodimerizes with BRCA1. It has been previously shown that BRCA1 binds to DNA, an interesting functional observation in light of the genetic data linking BRCA1 to DNA repair pathways. In this work, we reexamine the DNA-binding properties of BRCA1, comparing them with the DNA-binding properties of the BRCA1/BARD1 heterodimer. Because nuclear BRCA1 exists as a heterodimer with BARD1, it is likely that in vitro studies of …


Stiffness And Modulus And Independent Controllers Of Breast Cancer Metastasis, Dannielle Ryman Jan 2013

Stiffness And Modulus And Independent Controllers Of Breast Cancer Metastasis, Dannielle Ryman

Masters Theses 1911 - February 2014

One out of eight women in the United States will develop breast cancer during their lifetime. Ninety percent of cancer related deaths are due to metastasis. Metastasis is the biological process where individual or aggregate cancerous cells break away from the primary tumor site and colonize distant, non-adjacent locations throughout the body. It is my objectives to study how mechanical, topographical and biochemical cues affect metastatic breast cancer metastasis at an early developmental stage. ECM components have previously been shown to affect cell motility via ligand-receptor interactions, and physical cues, such as matrix stiffness and protein density. The primary tumor …


Examining The Functional Role Of Dprl-1 In Drosophila Melanogaster, John Valenzuela Jan 2013

Examining The Functional Role Of Dprl-1 In Drosophila Melanogaster, John Valenzuela

Summer Research

The Phosphatase of Regenerating Liver (PRL) family of proteins control cell growth, motility and proliferation. They have been shown to elevate the levels of these functions, leading to an increase in cancer metastasis (“malignancy”), when they are overexpressed. The goal of this experiment is to knockout PRL gene expression to examine the general function of PRL proteins. Drosophila melanogaster have only one copy of the PRL gene (dPRL-1), as opposed to humans and other mammals, which have 3. Thus, using P-element imprecise excision to create mutant strains either fully lacking or with decreased function of the dPRL-1 protein, …


Defining The Mechanism Of Enhanced Cellular Invasion Induced By Mechanical Stimulation, Snehal Sunil Ozarkar Jan 2013

Defining The Mechanism Of Enhanced Cellular Invasion Induced By Mechanical Stimulation, Snehal Sunil Ozarkar

Wayne State University Theses

Metastasis is a multistep process driven by various biochemical and mechanical factors, which eventually leads to formation of secondary tumors. The tumor mass is surrounded by basement membrane (BM) and stroma made of various extracellular matrix (ECM) proteins. During metastasis tumor cells disseminate from the primary tumor, breach the BM, invade the stroma, travel through blood and lymph and colonize tissues distant from the primary tumor. Formation of secondary tumors by metastasis is a leading cause of death in cancer patients. Even though plenty of research has been focused on biochemical factors affecting metastasis, information on role of mechanical factors …


Cancer Quasispecies And Stem-Like Adaptive Aneuploidy, Domenico Napoletani, M. Signore, Daniele C. Struppa Jan 2013

Cancer Quasispecies And Stem-Like Adaptive Aneuploidy, Domenico Napoletani, M. Signore, Daniele C. Struppa

Mathematics, Physics, and Computer Science Faculty Articles and Research

In this paper we develop a theoretical frame to understand self-regulation of aneuploidy rate in cancer and stem cells. This is accomplished building upon quasispecies theory, by leaving its formal mathematical structure intact, but by drastically changing the meaning of its objects. In particular, we propose a novel definition of chromosomal master sequence, as a sequence of physically distinct whole or fragmented chromosomes, whose length is taken to be the sum of the copy numbers of each whole or fragmented chromosome. This fundamental change in the functional objects of quasispecies theory allows us to show that previously measured aneuploidy rates …


Using Spheroids And A Bioluminescent Mouse Model To Determine The Effects Of Ajulemic Acid On Ewing's Scarcoma, Drake Hardy Jan 2013

Using Spheroids And A Bioluminescent Mouse Model To Determine The Effects Of Ajulemic Acid On Ewing's Scarcoma, Drake Hardy

Honors Theses

Ewing's Sarcoma is a pediatric bone cancer with a five-year survival rate of only 30%. New treatment options for this highly aggressive disease are desperately needed. Ajulemic acid (AJA), a synthetic cannabinoid, has been the focus of our research, and has demonstratedd the ability to decrease tumor cell viability and inhibit endothelial cell migration and angiogenesis. Based on these results, AJA is a potential therapeutic agent for Ewing's Sarcoma and other solid pediatric cancers. In order to create a realistic environment in vitro in which to study these tumors, we created 3-dimensional spheroids with three cell types, each of which …