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GSBS Dissertations and Theses

Apoptosis

Chemicals and Drugs

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Txnip Is A Mediator Of Er Stress-Induced Β-Cell Inflammation And Apoptosis: A Dissertation, Christine M. Oslowski May 2012

Txnip Is A Mediator Of Er Stress-Induced Β-Cell Inflammation And Apoptosis: A Dissertation, Christine M. Oslowski

GSBS Dissertations and Theses

Diabetes mellitus is a group of metabolic disorders characterized by hyperglycemia. The pathogenesis of these diseases involves β-cell dysfunction and death. The primary function of β-cells is to tightly regulate the secretion, production, and storage of insulin in response to blood glucose levels. In order to manage insulin biosynthesis, β-cells have an elaborate endoplasmic reticulum (ER).

The ER is an essential organelle for the proper processing and folding of proteins such as proinsulin. Proteins fold properly when the ER protein load balances with the ER folding capacity that handles this load. Disruption of this ER homeostasis by genetic and environmental ...


Dynamics Of Erythropoietic Survival Pathways In Vivo: A Dissertation, Miroslav Koulnis Jul 2011

Dynamics Of Erythropoietic Survival Pathways In Vivo: A Dissertation, Miroslav Koulnis

GSBS Dissertations and Theses

Erythropoiesis maintains stable tissue oxygenation in the basal state, while accelerating red cell production in anemia, blood loss or high altitude. The principal regulator of erythropoiesis is the hormone erythropoietin (Epo). In response to hypoxic stress, Epo can increase a 1000-fold, driving erythropoietic rate by up to 10-fold. It’s been suggested that survival pathways activated by the Epo receptor (EpoR) underlie its regulation of erythropoietic rate. A number of apparently redundant EpoR survival pathways were identified in vitro, raising the possibility of their functional specialization in vivo.

Here I assessed the roles of three survival pathways activated by EpoR ...


Regulation Of Cancer Cell Survival Mediated By Endogenous Tumor Suppression: A Dissertation, Minakshi Guha Jul 2009

Regulation Of Cancer Cell Survival Mediated By Endogenous Tumor Suppression: A Dissertation, Minakshi Guha

GSBS Dissertations and Theses

Cancer is the second leading cause of death among men and women after heart disease. Though our knowledge associated with the complexities of the cancer network has significantly improved over the past several decades, we have only recently started to get a more complete molecular understanding of the disease. To better comprehend signaling pathways that prevent disease development, we focused our efforts on investigating endogenous tumor suppression networks in controlling effectors of cancer cell survival and proliferation. Survivin is one such effector molecule that controls both cell proliferation and survival. In order to identify how this protein is overexpressed in ...


Defining The Role Of Ctbp2 In P53-Independent Tumor Suppressor Function Of Arf: A Dissertation, Ramesh C. Kovi Jun 2009

Defining The Role Of Ctbp2 In P53-Independent Tumor Suppressor Function Of Arf: A Dissertation, Ramesh C. Kovi

GSBS Dissertations and Theses

ARF, a potent tumor suppressor, positively regulates p53 by antagonizing MDM2, a negative regulator of p53, which in turn, results in either apoptosis or cell cycle arrest. ARF also suppresses the proliferation of cells lacking p53, and loss of ARF in p53-null mice, compared with ARF-null or p53-null mice, results in a broadened tumor spectrum and decreased tumor latency. This evidence suggests that ARF exerts both p53-dependent and p53-independent tumor suppressor activity. However, the molecular pathway and mechanism of ARF’s p53-independent tumor suppressor activity is not understood.

The antiapoptotic, metabolically regulated, transcriptional corepressor C-terminal binding protein 2 (CtBP2) has ...


Dna Damage-Induced Apoptosis In The Presence And Absence Of The Tumor Suppressor P53: A Dissertation, Laura Michelle Mcnamee Oct 2008

Dna Damage-Induced Apoptosis In The Presence And Absence Of The Tumor Suppressor P53: A Dissertation, Laura Michelle Mcnamee

GSBS Dissertations and Theses

A key regulator of DNA damage-induced apoptosis is the tumor suppressor gene, p53. p53 is a transcription factor that upregulates genes involved in cell cycle arrest, apoptosis, and senescence. How p53 decides to activate one of these responses in response to DNA damage is largely unanswered. Many have hypothesized it is due to interaction with various signaling pathways and post-translational modification. The p53 tumor suppressor can be modified by SUMO-1 in mammalian cells, but the functional consequences of this modification are unclear. Conjugation to SUMO is a reversible post-translational modification that regulates several transcription factors involved in cell proliferation, differentiation ...


Role Of Endoplasmic Reticulum Stress Response Signaling In T Cells: A Dissertation, Steven C. Pino Jul 2008

Role Of Endoplasmic Reticulum Stress Response Signaling In T Cells: A Dissertation, Steven C. Pino

GSBS Dissertations and Theses

T cells play a central role in cellular-mediated immunity and must become activated to participate as effector cells in the immune response. The activation process is highly intricate and involves stimulation of a number of downstream signaling pathways enabling T cells to proliferate and produce cytokines that are vital for proper effector function. This increase in protein production and protein folding activity adds to the normal physiological strain on cellular machinery. One cellular compartment that has generated a mechanism to mitigate the stress induced by increased protein production is the endoplasmic reticulum (ER).

In general, an increase in cellular production ...


Functional Analysis Of Ing1 And Ing4 In Cell Growth And Tumorigenesis: A Dissertation, Andrew H. Coles May 2008

Functional Analysis Of Ing1 And Ing4 In Cell Growth And Tumorigenesis: A Dissertation, Andrew H. Coles

GSBS Dissertations and Theses

The five member Inhibitor of Growth (ING) gene family has been proposed to participate in the regulation of cell growth, DNA repair, inflammation, chromatin remodeling, and tumor suppression. All ING proteins contain a PHD motif implicated in binding to methylated histones and are components of large chromatin remodeling complexes containing histone acetyltransferase (HAT) and histone deacetylase (HDAC) enzymes, suggesting a role for ING proteins in regulating gene transcription. Additionally, forced overexpression studies performed in vitro have indicated that several ING proteins can interact with the p53 tumor suppressor protein and/or the NF-кB protein complex. Since these two proteins play ...


Attrition Of Cd8 T Cells During The Early Stages Of Viral Infections: A Dissertation, Kapil Bahl Jan 2008

Attrition Of Cd8 T Cells During The Early Stages Of Viral Infections: A Dissertation, Kapil Bahl

GSBS Dissertations and Theses

Profound lymphopenia has been observed during many acute viral infections, and our laboratory has previously documented a type 1 IFN-dependent loss of most memory (CD44hi) and some naïve (CD44lo) CD8 T cells immediately preceding the development of the antiviral T cell response at days 2-4 following lymphocytic choriomeningitis virus (LCMV) infection. In this thesis, I will examine additional mechanisms involved in the early attrition of CD8 T cells and evaluate whether antigen-specific and non-specific CD8 T cells are equally susceptible. Lastly, I will examine whether the early attrition of CD8 T cells contributes to the generation of an ...


Pathways Linking Deregulated Proliferation To Apoptosis: A Dissertation, Harry A. Rogoff Apr 2004

Pathways Linking Deregulated Proliferation To Apoptosis: A Dissertation, Harry A. Rogoff

GSBS Dissertations and Theses

Proper regulation of cellular proliferation is critical for normal development and cancer prevention. Most, if not all, cancers contain mutations in the Rb/E2F pathway, which controls cellular proliferation. Inactivation of the retinoblastoma protein (Rb) can occur through Rb loss, mutation, or inactivation by cellular or viral oncoproteins leading to unrestrained proliferation. This occurs primarily by de-repression and activation of the E2F transcription factors, which promote the transition of cells from the G1to S phase of the cell cycle. In order to protect against loss of growth control, the p53 tumor suppressor is able to induce programmed cell ...


Stress Activated Protein Kinase Regulation Of Gene Expression In Apoptotic Neurons: A Dissertation, Gerard S. De Zutter Jul 2001

Stress Activated Protein Kinase Regulation Of Gene Expression In Apoptotic Neurons: A Dissertation, Gerard S. De Zutter

GSBS Dissertations and Theses

Summary

Basic biological processes require gene expression. Tightly regulated molecules known as transcription factors mediate the expression of genes in development and disease. Signal transduction pathways, which respond to environmental cues or stressors are major regulators of the transcription factors. Use of macromolecular synthesis inhibitors in models of normal neurodevelopment and neurodegenerative cell death has led to the discovery that gene expression is required for these processes to occur (Martin et. al.,(1988), J Cell Biol 106p829). To date, however, the identities of very few of the genes required in these events have been revealed. Hence, the activation or ...