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Glycopeptidome Of A Heavily N-Glycosylated Cell Surface Glycoprotein Of Dictyostelium Implicated In Cell Adhesion, Christa L. Feasley, Jennifer M. Johnson, Christopher M. West, Catherine P. Chia 2010 University of Oklahoma Health Sciences Center

Glycopeptidome Of A Heavily N-Glycosylated Cell Surface Glycoprotein Of Dictyostelium Implicated In Cell Adhesion, Christa L. Feasley, Jennifer M. Johnson, Christopher M. West, Catherine P. Chia

Faculty Publications in the Biological Sciences

Genetic analysis has implicated the cell surface glycoprotein gp130 in cell interactions of the social amoeba Dictyostelium, and information about the utilization of the 18 N-glycosylation sequons present in gp130 is needed to identify critical molecular determinants of its activity. Various glycomics strategies, including mass spectrometry of native and derivatized glycans, monosaccharide analysis, exoglycosidase digestion, and antibody binding, were applied to characterize a nonanchored version secreted from Dictyostelium. s-gp130 is modified by a predominant Man8GlcNAc4 species containing bisecting and intersecting GlcNAc residues and additional high-mannose N-glycans substituted with sulfate, methyl-phosphate, and/or core R3-fucose. Site mapping confirmed the occupancy of ...


Mult1e-Rgd Fusion Protein Drives Nk Cell-Mediated Anti-Tumor Response, Meg Steiner 2010 Clemson University

Mult1e-Rgd Fusion Protein Drives Nk Cell-Mediated Anti-Tumor Response, Meg Steiner

All Theses

A growing body of evidence indicates that natural killer (NK) cells are paramount to the identification and elimination of cancerous and pre-cancerous cells during normal immunosurveillance. In addition, NK cells provide a vital link between the innate and adaptive immune systems during an anti-tumoral response. In the present study, a novel fusion protein was designed from the extracellular portion of mouse UL16-binding protein-like transcript 1 (MULT1), a ligand for the activating NKG2D receptor on NK cells, and a short arginine-glycine-aspartic acid (RGD) -containing peptide, which binds the integrin αvβ3 of tumor-specific neovasculature. In vitro studies showed that the fusion protein ...


Myogenin Modulates Exercise Endurance By Altering Skeletal Muscle Metabolism, james eric meadows 2010 University of Texas Graduate School of Biomedical Sciences at Houston

Myogenin Modulates Exercise Endurance By Altering Skeletal Muscle Metabolism, James Eric Meadows

UT GSBS Dissertations and Theses (Open Access)

The function of myogenic regulatory factors (MRFs) during adult life is not well understood. The requirement of one of these MRFs, myogenin (Myog), during embryonic muscle development suggests an equally important role in adult muscle. In this study, we have determined the function of myogenin during adult life using a conditional allele of Myog. In contrast to embryonic development, myogenin is not required for adult viability, and Myog-deleted mice exhibited no remarkable phenotypic changes during sedentary life. Remarkably, sedentary Myog-deleted mice demonstrated enhanced exercise endurance during involuntary treadmill running. Altered blood glucose and lactate levels in sedentary Myog-deleted mice after ...


Smooth Muscle Hyperplasia Due To Acta2/Myh11 Mutations: Identification Of Novel Pathology And Pathways Leading To Aneurysms And Diverse Vascular Occlusive Diseases, Christina L. Papke 2010 University of Texas Graduate School of Biomedical Sciences at Houston

Smooth Muscle Hyperplasia Due To Acta2/Myh11 Mutations: Identification Of Novel Pathology And Pathways Leading To Aneurysms And Diverse Vascular Occlusive Diseases, Christina L. Papke

UT GSBS Dissertations and Theses (Open Access)

Missense mutations in smooth muscle cell (SMC) specific ACTA2 (á-actin) and MYH11 (â-myosin heavy chain) cause diffuse and diverse vascular diseases, including thoracic aortic aneurysms and dissections (TAAD) and early onset coronary artery disease and stroke. The mechanism by which these mutations lead to dilatation of some arteries but occlusion of others is unknown. We hypothesized that the mutations act through two distinct mechanisms to cause varied vascular diseases: a loss of function, leading to decreased SMC contraction and aneurysms, and a gain of function, leading to increased SMC proliferation and occlusive disease. To test this hypothesis, ACTA2 mutant SMCs ...


The Consequences Of Disrupting The Mdm2-P53 Balance In Hematopoiesis, Hussein A. Abbas 2010 University of Texas Graduate School of Biomedical Sciences at Houston

The Consequences Of Disrupting The Mdm2-P53 Balance In Hematopoiesis, Hussein A. Abbas

UT GSBS Dissertations and Theses (Open Access)

The bone marrow accommodates hematopoietic stem cells and progenitors. These cells provide an indispensible resource for replenishing the blood constituents throughout an organism’s life. A tissue with such a high turn-over rate mandates intact cycling checkpoint and apoptotic pathways to avoid inappropriate cell proliferation and ultimately the development of leukemias. p53, a major tumor suppressor, is a transcription factor that regulates cell cycle, and induces apoptosis and senescence. Mice inheriting a hypomorphic p53 allele in the absence of Mdm2, a p53 inhibitor, have elevated p53 cell cycle activity and die by postnatal day 13 due to hematopoietic failure. Hematopoiesis ...


Survival Prediction For Brain Tumor Patients Using Gene Expression Data, Vinicius Bonato 2010 University of Texas Graduate School of Biomedical Sciences at Houston

Survival Prediction For Brain Tumor Patients Using Gene Expression Data, Vinicius Bonato

UT GSBS Dissertations and Theses (Open Access)

Brain tumor is one of the most aggressive types of cancer in humans, with an estimated median survival time of 12 months and only 4% of the patients surviving more than 5 years after disease diagnosis. Until recently, brain tumor prognosis has been based only on clinical information such as tumor grade and patient age, but there are reports indicating that molecular profiling of gliomas can reveal subgroups of patients with distinct survival rates. We hypothesize that coupling molecular profiling of brain tumors with clinical information might improve predictions of patient survival time and, consequently, better guide future treatment decisions ...


New Target Genes For Tumor Suppressors P53 And P73 In Regenerating Liver, Svitlana M. Kurinna 2010 University of Texas Graduate School of Biomedical Sciences at Houston

New Target Genes For Tumor Suppressors P53 And P73 In Regenerating Liver, Svitlana M. Kurinna

UT GSBS Dissertations and Theses (Open Access)

The p53-family of proteins regulates expression of target genes during tissue development and differentiation. Within the p53-family, p53 and p73 have hepatic-specific functions in development and tumor suppression. Despite a growing list of p53/p73 target genes, very few of these have been studied in vivo, and the knowledge regarding functions of p53 and p73 in normal tissues remains limited. p53+/-p73+/- mice develop hepatocellular carcinoma (HCC), whereas overexpression of p53 in human HCC leads to tumor regression. However, the mechanism of p53/p73 function in liver remains poorly characterized. Here, the model of mouse liver regeneration is used to ...


Delta Like Ligand 4 Is A Critical Regulator Of Bone Marrow Cell Differentiation Into Pericytes/Vascular Smooth Muscle Cells And Is Essential For The Vasculogenesis That Supports The Growth Of Ewing’S Sarcoma, Keri L. Stewart 2010 University of Texas Graduate School of Biomedical Sciences at Houston

Delta Like Ligand 4 Is A Critical Regulator Of Bone Marrow Cell Differentiation Into Pericytes/Vascular Smooth Muscle Cells And Is Essential For The Vasculogenesis That Supports The Growth Of Ewing’S Sarcoma, Keri L. Stewart

UT GSBS Dissertations and Theses (Open Access)

We have previously shown that vasculogenesis, the process by which bone marrow-derived cells are recruited to the tumor and organized to form a blood vessel network de novo, is essential for the growth of Ewing’s sarcoma. We further demonstrated that these bone marrow cells differentiate into pericytes/vascular smooth muscle cells(vSMC) and contribute to the formation of the functional vascular network. The molecular mechanisms that control bone marrow cell differentiation into pericytes/vSMC in Ewing’s sarcoma are poorly understood. Here, we demonstrate that the Notch ligand Delta like ligand 4 (DLL4) plays a critical role in this ...


Mechanism-Based Strategies To Enhance The Actions Of A, fabiola c. gomez 2010 University of Texas Graduate School of Biomedical Sciences at Houston

Mechanism-Based Strategies To Enhance The Actions Of A, Fabiola C. Gomez

UT GSBS Dissertations and Theses (Open Access)

Heat shock protein 90 (HSP90) is an abundant molecular chaperone that regulates the functional stability of client oncoproteins, such as STAT3, Raf-1 and Akt, which play a role in the survival of malignant cells. The chaperone function of HSP90 is driven by the binding and hydrolysis of ATP. The geldanamycin analog, 17-AAG, binds to the ATP pocket of HSP90 leading to the degradation of client proteins. However, treatment with 17-AAG results in the elevation of the levels of antiapoptotic proteins HSP70 and HSP27, which may lead to cell death resistance. The increase in HSP70 and HSP27 protein levels is due ...


Cip4 And Src In Promoting The Migration And Invasion Of Breast Cancers, Christina S. Pichot 2010 University of Texas Graduate School of Biomedical Sciences at Houston

Cip4 And Src In Promoting The Migration And Invasion Of Breast Cancers, Christina S. Pichot

UT GSBS Dissertations and Theses (Open Access)

Cellular invasion represents a critical early step in the metastatic cascade, and many proteins have been identified as part of an “invasive signature.” The non-receptor tyrosine kinase Src is commonly upregulated in breast cancers, often in conjunction with overexpression of EGFR. Signaling from this pathway stimulates cell proliferation, migration, and invasion and frequently involves proteins that regulate the cytoskeleton. My data demonstrates that inhibition of Src, using the small-molecule inhibitor dasatinib, impairs cellular migration and invasion. Furthermore, Src inhibition sensitizes the cells to the effects of the chemotherapeutic doxorubicin resulting in dramatic, synergistic inhibition of proliferation with combination treatments. The ...


Inhibition Of Deubiquitinase Activity And Ubiquitination Of Jak2 Blocks Cytokine Signaling And Induces Tumor Cell Apoptosis, Vaibhav Kapuria 2010 University of Texas Graduate School of Biomedical Sciences at Houston

Inhibition Of Deubiquitinase Activity And Ubiquitination Of Jak2 Blocks Cytokine Signaling And Induces Tumor Cell Apoptosis, Vaibhav Kapuria

UT GSBS Dissertations and Theses (Open Access)

The Jak-stat pathway is critical for cellular proliferation and is commonly found to be deregulated in many solid tumors as well as hematological malignancies. Such findings have spurred the development of novel therapeutic agents that specifically inhibit Jak2 kinase, thereby suppressing tumor cell growth. Tyrphostin AG490, the first described Jak2 inhibitor, displays poor pharmacology and requires high concentrations for anti-tumor activities. Our research group screened a small library of AG490 structural analogues and identified WP1130 as a potent inhibitor of Jak2 signaling. However, unlike AG490, WP1130 did not directly inhibit Jak2 kinase activity. Our results show that WP1130 induces rapid ...


The Ubiquitin Ligase Ube4b Is Required For Efficient Epidermal Growth Factor Receptor Degradation, Natalie Sirisaengtaksin 2010 University of Texas Graduate School of Biomedical Sciences at Houston

The Ubiquitin Ligase Ube4b Is Required For Efficient Epidermal Growth Factor Receptor Degradation, Natalie Sirisaengtaksin

UT GSBS Dissertations and Theses (Open Access)

The length of time that integral membrane proteins reside on the plasma membrane is regulated by endocytosis, a process that can inactivate these proteins by removing them from the membrane and may ultimately result in their degradation. Proteins are internalized and pass through multiple distinct intracellular compartments where targeting decisions determine their fate. Membrane proteins initially enter early endosomes, and subsequently late endosomes/multivesicular bodies (MVBs), before being degraded in the lysosome. The MVB is a subset of late endosomes characterized by the appearance of small vesicles in its luminal compartment. These vesicles contain cargo proteins sorted from the limiting ...


Cellular And Developmental Functions Of The Xenopus Arvcf-Catenin:Kazrin Complex, Kyucheol Cho 2010 The Texas Medical Center Library

Cellular And Developmental Functions Of The Xenopus Arvcf-Catenin:Kazrin Complex, Kyucheol Cho

UT GSBS Dissertations and Theses (Open Access)

Xenopus ARVCF (xARVCF), a member of p120-catenin subfamily, binds cadherin cytoplasmic domains to enhance cadherin metabolic stability, or when dissociated, modulates Rho-family GTPases. We previously found that xARVCF binds directly to Xenopus KazrinA (xKazrinA), a widely expressed, conserved protein that bears little homology to established protein families. xKazrinA is also known to influence keratinocyte proliferation-differentiation and cytoskeletal activity. In my study, I first evaluated the expression pattern of endogenous Kazrin RNA and protein in Xenopus embryogenesis as well as in adult tissues. We then collaboratively predicted the helical structure of Kazrin’s coiled-coil domain, and I obtained evidence of Kazrin ...


Xenoestrogen-Specific Mechanisms Of Developmental Reprogramming Correlate With Gene Expression And Tumor Development, Kristen L. Greathouse 2010 University of Texas Graduate School of Biomedical Sciences at Houston

Xenoestrogen-Specific Mechanisms Of Developmental Reprogramming Correlate With Gene Expression And Tumor Development, Kristen L. Greathouse

UT GSBS Dissertations and Theses (Open Access)

Environmental exposures during sensitive windows of development can reprogram normal physiological responses and alter disease susceptibility later in life in a process known as developmental reprogramming. We have shown that neonatal exposure to the xenoestrogen diethylstilbestrol (DES) can developmentally reprogram the reproductive tract in genetically susceptible Eker rats giving rise to complete penetrance of uterine leiomyoma. Based on this, we hypothesized that xenoestrogens, including genistein (GEN) and bisphenol A (BPA), reprogram estrogen-responsive gene expression in the myometrium and promote the development of uterine leiomyoma. We proposed the mechanism that is responsible for the developmental reprogramming of gene expression was through ...


Validation Of The Activation Of Aurora B Kinase By Caenorhabditis Elegans Tousled-Like Kinase And The Identification Of Cyclin B3 As A Phospho-Specific Tlk-1 Interactor, Gary Michael Deyter 2010 University of Texas Graduate School of Biomedical Sciences at Houston

Validation Of The Activation Of Aurora B Kinase By Caenorhabditis Elegans Tousled-Like Kinase And The Identification Of Cyclin B3 As A Phospho-Specific Tlk-1 Interactor, Gary Michael Deyter

UT GSBS Dissertations and Theses (Open Access)

A hallmark of tumorigenesis and certain birth defect syndromes is the loss of ploidy that can result from incorrect chromosome segregation. Chromosomes that are not partitioned properly during mitosis are often fragmented, changing the genetic makeup of daughter cells. Inheriting extrachromosomal fragments that contain cell survival genes or losing chromosomal loci that encode tumor suppressors can promote tumor development. Thus, it is essential to elucidate molecular mechanisms required for correct chromosome segregation. Chromosomes are connected to mitotic spindle microtubules by way of a proteinacous, chromosome-bound organelle called the kinetochore. Two decades of research have confirmed that the conserved Aurora B ...


From Mouse Mammary Tumor Model To New Therapeutic Method ---Mammary Tumor Development In Balb/C-Trp53+/- Mice And Magnetic Nanoparticle Induced Heating For Cancer Treatment, Haoheng Yan 2010 University of Massachusetts Amherst

From Mouse Mammary Tumor Model To New Therapeutic Method ---Mammary Tumor Development In Balb/C-Trp53+/- Mice And Magnetic Nanoparticle Induced Heating For Cancer Treatment, Haoheng Yan

Open Access Dissertations

PATHWAYS CONTRIBUTING TO DEVELOPMENT OF SPONTANEOUS MAMMARY TUMORS IN BALB/c-Trp53+/- MICE Mutation and loss of p53 function are common features among human breast cancers. We use BALB/c-Trp53+/- mice as a model to examine the sequence of events leading to mammary tumors. Mammary epithelium proliferation rates were similar in both BALB/c-Trp53+/- mice and wild type controls. Among the 28 mammary tumors collected from BALB/c-Trp53+/- mice, loss of heterozygosity for Trp53 was detected in more than 90% of invasive mammary tumors. Transplantation of Trp53+/- ductal hyperplasias indicated an association between loss of the wild type allele of Trp53 ...


Notch 1 Mediated Inhibition Of Nur77-Induced Apoptosis: Implications For T-Cell Leukemia, Jonathan George Rud 2010 University of Massachusetts Amherst

Notch 1 Mediated Inhibition Of Nur77-Induced Apoptosis: Implications For T-Cell Leukemia, Jonathan George Rud

Open Access Dissertations

It is widely accepted that activating mutations of genes encoding the Notch family of transmembrane receptors, specifically Notch1, are associated with oncogenic transformation. Previous data from our lab has shown that an active form of Notch1 (NICD) provides protection against apoptosis in D011.10 T cells; and that this effect may be attributed to NICD binding the pro-apoptotic protein Nur77. Nur77 is an immediate early gene that is upregulated during both negative selection of thymocytes and activation-induced apoptosis in D011.10 T cells. Nur77 upregulation is tightly regulated and requires MEF2D, NFAT, and the transcriptional co-activator, p300, to effectively respond ...


Midterm Outcomes Of Autologous Cultivated Limbal Stem Cell Transplantation With Or Without Penetrating Keratoplasty, Hossein Baharvand 2010 university of science & culture

Midterm Outcomes Of Autologous Cultivated Limbal Stem Cell Transplantation With Or Without Penetrating Keratoplasty, Hossein Baharvand

university of science & culture

To report the midterm outcomes of autologous limbal stem cell transplantation cultivated on amniotic membrane (AM) with or without subsequent penetrating keratoplasty (PKP) in patients with total unilateral limbal stem cell deficiency (LSCD). Methods: Eight eyes of 8 consecutive patients with unilateral total LSCD underwent autologous limbal stem cell transplantation cultivated on AM. Four eyes underwent subsequent optical PKP. Main outcome measures were corneal vascularization and transparency. Results: The patients were followed for 34.0 6 13.5 months (6–48 months). Seven cases had a stable corneal epithelium with marked decrease in opacification and vascularization. Progressive sectorial conjunctivalization was ...


Acetylation Of Wrn Protein Regulates Its Stability By Inhibiting Ubiquitination, Kai Li, Rui Wang, Enerlyn M. Lozada, Wei Fan, David K. Orren, Jianyuan Luo 2010 University of Massachusetts Medical School

Acetylation Of Wrn Protein Regulates Its Stability By Inhibiting Ubiquitination, Kai Li, Rui Wang, Enerlyn M. Lozada, Wei Fan, David K. Orren, Jianyuan Luo

Open Access Articles

BACKGROUND: WRN is a multi-functional protein involving DNA replication, recombination and repair. WRN acetylation has been demonstrated playing an important role in response to DNA damage. We previously found that WRN acetylation can regulate its enzymatic activities and nuclear distribution.

METHODOLOGY/PRINCIPAL FINDING: Here, we investigated the factors involved in WRN acetylation and found that CBP and p300 are the only major acetyltransferases for WRN acetylation. We further identified 6 lysine residues in WRN that are subject to acetylation. Interestingly, WRN acetylation can increase its protein stability. SIRT1-mediated deacetylation of WRN reverses this effect. CBP dramatically increases the half-life of ...


Temporal Regulation Of The Muscle Gene Cascade By Macho1 And Tbx6 Transcription Factors In Ciona Intestinalis, Jamie E. Kugler, Stefan Gazdoiu, Izumi Oda-Ishii, Yale J. Passamaneck, Albert J. Erives, Anna Di Gregorio 2010 Cornell University

Temporal Regulation Of The Muscle Gene Cascade By Macho1 And Tbx6 Transcription Factors In Ciona Intestinalis, Jamie E. Kugler, Stefan Gazdoiu, Izumi Oda-Ishii, Yale J. Passamaneck, Albert J. Erives, Anna Di Gregorio

Open Dartmouth: Faculty Open Access Articles

For over a century, muscle formation in the ascidian embryo has been representative of 'mosaic' development. The molecular basis of muscle-fate predetermination has been partly elucidated with the discovery of Macho1, a maternal zinc-finger transcription factor necessary and sufficient for primary muscle development, and of its transcriptional intermediaries Tbx6b and Tbx6c. However, the molecular mechanisms by which the maternal information is decoded by cis-regulatory modules (CRMs) associated with muscle transcription factor and structural genes, and the ways by which a seamless transition from maternal to zygotic transcription is ensured, are still mostly unclear. By combining misexpression assays with CRM analyses ...


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