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Autophagy

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Full-Text Articles in Cell Biology

Elucidating Immune Signaling Of Influenza A Virus And Aspergillus Fumigatus Co-Infections Through Pioneered Model Development, Meagan Danyelle Rippee-Brooks Jan 2019

Elucidating Immune Signaling Of Influenza A Virus And Aspergillus Fumigatus Co-Infections Through Pioneered Model Development, Meagan Danyelle Rippee-Brooks

MSU Graduate Theses

Bacterial co-infections with influenza A virus (IAV) are extremely serious and life-threatening. However, there exists limited understanding about the importance of fungal infections with IAV. Clinical case reports indicate that fungal co-infections do occur and suggest the IAV pandemic of 2009 had a propensity to predispose patients to secondary fungal infections more than previous IAV strains. IAV-fungal co-infections are marked by high mortality rates of 47 to 61% in previously healthy individuals between the ages of 20 and 60. Yet, the variables involved in this co-infection remain undetermined. I achieved effective recapitulation of this co-infection using a C57Bl/6 murine ...


Role Of Jip1-Jnk Signaling In Beta-Cell Function And Autophagy, Seda Barutcu Jan 2018

Role Of Jip1-Jnk Signaling In Beta-Cell Function And Autophagy, Seda Barutcu

GSBS Dissertations and Theses

Proper functioning of endocrine cells is crucial for organismal homeostasis. The underlying mechanisms that fine-tune the amount, and the timing of hormone secretion are not clear. JIP1 / MAPK8IP1 (JNK interacting protein 1) is a scaffold protein that mediates cellular stress response, and is highly expressed in endocrine cells, including insulin secreting b-cells in pancreas islets. However, the role of JIP1 in b-cells is unclear. This study demonstrates that b-cell specific Jip1 ablation results in decreased glucose-induced insulin secretion, without a change in Insulin1 and Insulin2 gene expression. Inhibition of both JIP1-kinesin interaction, and JIP1-JNK interaction by genetic mutations also resulted ...


Investigating Autophagy, Extracellular Vesicles, And Glycobiology, Benjamin Cook Jan 2018

Investigating Autophagy, Extracellular Vesicles, And Glycobiology, Benjamin Cook

Master's Theses

Autophagy is a cellular process of degradation which degrades cellular materials in acidic organelles called lysosomes. Impairment of lysosomal degradation can lead to lysosomal storage disorders such as Parkinson's Disease. In Parkinson's Disease neurotoxic α-synuclein can spread from cell-to-cell via extracellular vesicles. We investigated the changes in extra vesicular glycans upon perturbation of autophagy using a class of glycan binding molecules termed lectins.

We found that upon induction of autophagy causes EV glycans to increase while others remained consistent. Additionally, we found that specific glycans are increased more than others. Conversely, when lysosomal degradation was impaired, we ...


Mechanisms Underlying The Sensitivity And Resistance Of Gastric Cancer Cells To Met Inhibitors, Rebecca Schroeder Aug 2017

Mechanisms Underlying The Sensitivity And Resistance Of Gastric Cancer Cells To Met Inhibitors, Rebecca Schroeder

UT GSBS Dissertations and Theses (Open Access)

MET amplification has been clinically credentialed as a therapeutic target in gastric cancer, but the molecular mechanisms underlying sensitivity and resistance to MET inhibitors are still not well understood. Using whole-genome mRNA expression profiling, we identified autophagy as a top molecular pathway that was activated by the MET inhibitor crizotinib in drug-sensitive human gastric cancer cells, and functional studies confirmed that crizotinib increased autophagy levels in the drug sensitive cells in a concentration-dependent manner. We then used chemical and molecular approaches to inhibit autophagy in order to define its role in cell death. The clinically available inhibitor of autophagy, chloroquine ...


Complement-Related Regulates Autophagy In Neighboring Cells, Lin Lin Jun 2017

Complement-Related Regulates Autophagy In Neighboring Cells, Lin Lin

GSBS Dissertations and Theses

Autophagy is a conserved process that cells use to degrade their own cytoplasmic components by delivery to lysosomes. Autophagy ensures intracellular quality control and is associated with diseases such as cancer and immune disorders. The process of autophagy is controlled by core autophagy (Atg) genes that are conserved from yeast to mammal. Most Atg proteins and their regulators were identified through pioneering studies of the single cell yeast Saccharomyces cerevisiae, and little is known about factors that systematically coordinate autophagy within the tissues of multicellular animals. The goal of this thesis is to identify new autophagy regulators and provide a ...


The Recycling Gtpase, Rab-10, Regulates Autophagy Flux In Caenorhabditis Elegans, Nicholas J. Palmisano Jun 2017

The Recycling Gtpase, Rab-10, Regulates Autophagy Flux In Caenorhabditis Elegans, Nicholas J. Palmisano

All Dissertations, Theses, and Capstone Projects

Autophagy and endocytosis are two cellular pathways that are vital to cell growth and homeostasis. Autophagy is a dynamic and catabolic process involving the formation of a double-membrane vesicle called the autophagosome, which engulfs long-lived proteins and damaged organelles. Endocytosis involves the uptake of extracellular material into the cell through the formation of intracellular vesicles termed endosomes. Although both endocytosis and autophagy are interconnected processes, the extent to which endocytic proteins and/or compartments contribute to autophagy, and how these endocytic components do so, is still unknown. To improve our understanding of the connections that exist between autophagy and endocytosis ...


The Regulation Of Rotavirus–Infected Ht29.F8 And Ma104 Cells Treated With Arachidin 1 Or Arachidin 3, Caleb M. Witcher May 2017

The Regulation Of Rotavirus–Infected Ht29.F8 And Ma104 Cells Treated With Arachidin 1 Or Arachidin 3, Caleb M. Witcher

Electronic Theses and Dissertations

Rotavirus (RV) infections cause severe life threatening diarrhea in young children and immunocompromised individuals. Several effective vaccines have been developed for young children but are not protective against all strains of RV, and there are no anti-RV therapeutics. Our laboratory has discovered a decrease in the number of infectious simian RV particles (SA114f) in human intestinal cell line, HT29.f8 cells with the addition of either of two stilbenoids, arachidin-1 (A1) or arachidin-3 (A3). This suggests effects on the host cell and RV replication. We examined the cellular effects of human RV strain (Wa) on a human intestinal cell line ...


Pam-1 Localizations In The Regulation Of Autophagy During Caenorhabditis Elegans Oogenesis, Ashley Munie May 2017

Pam-1 Localizations In The Regulation Of Autophagy During Caenorhabditis Elegans Oogenesis, Ashley Munie

Honors College Theses

Autophagy, the cell's recycling system, is a highly-conserved survival mechanism of the cell. Autophagy has been implicated in the mediation of the removal of cytotoxic aggregates, such as those linked to neurodegenerative disorders like Huntington and Alzheimer disease. Studies in several model organisms have identified numerous genes involved in mediating autophagy, including the Puromycin sensitive aminopeptidase (Psa). The Caenorhabditis elegans orthologue of Psa, pam-1, also governs fertility. Along with apoptosis, a form of regulated cell death, autophagy has been found to be required for efficient C. elegans oogenesis. When autophagy is suppressed through RNAi in worms harboring a pam-1 ...


The Role Of The Diras Family Members In Regulating Ras Function, Cancer Growth And Autophagy, Margie Nicole Sutton May 2017

The Role Of The Diras Family Members In Regulating Ras Function, Cancer Growth And Autophagy, Margie Nicole Sutton

UT GSBS Dissertations and Theses (Open Access)

DIRAS3 is a maternally imprinted tumor suppressor gene that is downregulated by multiple mechanisms across several tumor types. When re-expressed, DIRAS3 decreases proliferation, inhibits motility, and induces autophagy and tumor dormancy. DIRAS3 encodes a 26 kDa small GTPase with 60% homology to Ras and Rap, differing from oncogenic Ras family members by a 34-amino acid N-terminal extension that is required for its tumor suppressive function in ovarian cancer. By assessing the structure-function relationship, I found that DIRAS3 inhibits Ras-induced transformation and is a natural antagonist of Ras/MAPK signaling. DIRAS3 binds directly to Ras and disrupts cluster formation inhibiting the ...


Characterizing A Signaling Network That Maintains Hematopoietic Stem Cells, Michelle Nguyen-Mccarty Jan 2017

Characterizing A Signaling Network That Maintains Hematopoietic Stem Cells, Michelle Nguyen-Mccarty

Publicly Accessible Penn Dissertations

Hematopoietic stem cells (HSCs) are able to self-renew and to differentiate into all blood cells. HSCs reside in a low-perfusion niche and depend on local signals to survive and to maintain the capacity for self-renewal. HSCs removed from the niche can survive if they receive hematopoietic cytokines, but they then lose the ability to self-renew. However, we showed previously that simultaneous inhibition of glycogen synthase kinase-3 (GSK-3) and mammalian target of rapamycin complex 1 (mTORC1) maintains HSC function ex vivo without the need for exogenous cytokines. As these experiments were initially done in heterogeneous cell populations, I then showed that ...


Two Components Of Maintaining Developmental Competence: Microrna-21 In The Maturing Oocyte And Autophagy Induction In The Follicular Stage Ovary, Benjamin J. Hale Jan 2017

Two Components Of Maintaining Developmental Competence: Microrna-21 In The Maturing Oocyte And Autophagy Induction In The Follicular Stage Ovary, Benjamin J. Hale

Graduate Theses and Dissertations

This dissertation describes two processes that the oocyte and ovary potentially utilize to maintain reproductive competence: autophagy in response to heat stress and microRNA-21 function during meiotic maturation. Heat stress (HS) occurs when heat accumulation (from internal and external sources) exceeds heat dissipation. HS is associated with seasonal infertility and therefore is a production issue and profitability constraint in the swine industry. Autophagy is the process by which somatic cells recycle cellular components and it is activated by a variety of stressors. Therefore, characterizing autophagy in the ovary and oocyte is valuable because of the potential of autophagy to mitigate ...


Interaction Between Regulation Of Autophagy, Stress Responses And Growth In Arabidopsis Thaliana, Yunting Pu Jan 2017

Interaction Between Regulation Of Autophagy, Stress Responses And Growth In Arabidopsis Thaliana, Yunting Pu

Graduate Theses and Dissertations

Plants have evolved sophisticated mechanisms to balance between growth and stress tolerance upon changing environmental conditions. Autophagy is a critical process for recycling of cytoplasmic materials during nutrient remodeling and stress responses. Upon activation, the materials to be degraded are engulfed by a double-membrane vesicle called an autophagosome, which delivers the cargo to the vacuole for degradation and recycling. Studies in plants have revealed genes that are involved in the core machinery of autophagosome formation and delivery, and key regulators of autophagy. However, the upstream regulators of autophagy and the functions of autophagy in balancing growth and stress tolerance remain ...


Axonal Transport And Life Cycle Of Mitochondria In Parkinson's Disease Model, Hyun Sung Apr 2016

Axonal Transport And Life Cycle Of Mitochondria In Parkinson's Disease Model, Hyun Sung

Open Access Dissertations

In neurons, normal distribution and selective removal of mitochondria are essential for preserving compartmentalized cellular function. Parkin, an E3 ubiquitin ligase associated with familial Parkinson’s disease, has been implicated in mitochondrial dynamics and removal. However, it is not clear how Parkin plays a role in mitochondrial turnover in vivo, and whether the mature neurons possess a compartmentalized Parkin-dependent mitochondrial life cycle. Using the live Drosophila nervous system, here, I investigate the involvement of Parkin in mitochondrial dynamics; organelle distribution, morphology and removal. Parkin deficient animals displayed less number of axonal mitochondria without disturbing organelle motility behaviors, morphology and metabolic ...


Leptin Regulates The Expression Of Autophagy-Related Genes In Chickens, Peter Olawale Ishola Dec 2015

Leptin Regulates The Expression Of Autophagy-Related Genes In Chickens, Peter Olawale Ishola

Theses and Dissertations

Autophagy or cellular self-digestion, a lysosomal degradation pathway that is conserved from yeast to human, plays a key role in recycling cellular constituents, including damaged organelles. It also plays a pivotal role in the adaptation of cells to a plethora of distinct stressors including starvation. Autophagy has been extensively studied in mammals and yeast, but little is known in avian species. Thus, the major objective of the present study was to determine the effects of leptin on autophagy-related genes in chicken hypothalamus, muscle and liver. Leptin is an adipocytokine that is mostly produced by white adipose cells in mammals (as ...


Role And Regulation Of Autophagy During Developmental Cell Death In Drosophila Melanogaster: A Dissertation, Kirsten M. Tracy Apr 2015

Role And Regulation Of Autophagy During Developmental Cell Death In Drosophila Melanogaster: A Dissertation, Kirsten M. Tracy

GSBS Dissertations and Theses

Autophagy is a conserved catabolic process that traffics cellular components to the lysosome for degradation. Autophagy is required for cell survival during nutrient restriction, but it has also been implicated in programmed cell death. It is associated with several diseases, including cancer. Cancer is a disease characterized by aberrant cell growth and proliferation. To support this growth, the tumor cell often deregulates several metabolic processes, including autophagy. Interestingly, autophagy plays paradoxical roles in tumorigenesis. It has been shown to be both tumor suppressive through cell death mechanisms and tumor promoting through its cytoprotective properties. However, the mechanisms regulating the balance ...


Microrna Regulation Of Autophagy During Programmed Cell Death: A Dissertation, Charles J. Nelson Mar 2015

Microrna Regulation Of Autophagy During Programmed Cell Death: A Dissertation, Charles J. Nelson

GSBS Dissertations and Theses

Autophagy delivers cytoplasmic material to the lysosome for degradation, and has been implicated in many cellular processes, including stress, infection, survival, and death. Although the regulation and role that autophagy plays in stress, infection, and survival is apparent, its involvement during cell death remains relatively unclear. In this thesis I summarize what is known about the roles autophagy can play in cell death, and the differences between the utilization of autophagy during nutrient deprivation and cell death. Utilizing Drosophila melanogaster as a model system, the roles autophagy plays in both of these contexts can be studied. The goal of this ...


Autophagy-Independent Role For Beclin 1 In The Regulation Of Growth Factor Receptor Signaling: A Dissertation, Rasika Rohatgi Jan 2015

Autophagy-Independent Role For Beclin 1 In The Regulation Of Growth Factor Receptor Signaling: A Dissertation, Rasika Rohatgi

GSBS Dissertations and Theses

Beclin 1 is a haplo-insufficient tumor suppressor that is decreased in many human tumors. The function of Beclin 1 in cancer has been attributed primarily to its role in the degradative process of autophagy. However, the role of autophagy itself in tumorigenesis is context-dependent and can be both preventive and promoting. Due to its dual function in cancer a better understanding of this process is necessary to develop potential novel cancer therapies. To gain insight into the role of autophagy in breast carcinoma, I analyzed the autophagydependency of different subtypes of breast cancer. My results implicate that triple-negative breast carcinoma ...


Targeting Stress Response Pathways In Soft Tissue Sarcoma: The Role Of Hypoxia And Autophagy In Tumor Survival, Michael Nakazawa Jan 2015

Targeting Stress Response Pathways In Soft Tissue Sarcoma: The Role Of Hypoxia And Autophagy In Tumor Survival, Michael Nakazawa

Publicly Accessible Penn Dissertations

Soft tissue sarcomas (STS) are a group of malignancies that arise from mesenchymal tissue, consisting of over 50 distinct histiologic subtypes. Unfortunately, the five-year survival rate of sarcoma patients has remained relatively unchanged, and due to the rarity of the disease, research and development of adequate therapeutics for STS lags behind other cancers. Therefore, understanding the molecular drivers of STS is important in developing new therapeutics, as well as discovering druggable processes that occur across multiple subtypes. One feature common to STS is hypoxia, or low O2 conditions. Using molecular biology, biochemical approaches, genetically engineered mouse models, as well as ...


Defective Autophagy In Neurodegeneration: Novel Roles For Huntingtin And Optineurin In Regulating Autophagosome Dynamics, Chyi Haw Yvette Wong Jan 2015

Defective Autophagy In Neurodegeneration: Novel Roles For Huntingtin And Optineurin In Regulating Autophagosome Dynamics, Chyi Haw Yvette Wong

Publicly Accessible Penn Dissertations

Autophagy is an essential cellular degradative process that has been implicated in the pathogenesis of several neurodegenerative diseases including Huntington's disease and Amyotrophic Lateral Sclerosis (ALS). During autophagy, autophagosomes form around cargo such as mitochondria, and subsequently fuse with lysosomes to acidify and acquire enzymes to degrade internalized cargos. In neurons, constitutive autophagosome biogenesis preferentially occurs at the axon tip, followed by the robust retrograde axonal transport of autophagosomes back to the cell body. The mechanisms regulating both the axonal transport of autophagosomes and the selective degradation of damaged mitochondria have not yet been determined. Here, I report novel ...


Strategies To Sensitize Bladder Cancer Cells To Small Molecule Inhibitors Targeting The Pi3k Pathway, Giovanni Nitti Aug 2014

Strategies To Sensitize Bladder Cancer Cells To Small Molecule Inhibitors Targeting The Pi3k Pathway, Giovanni Nitti

UT GSBS Dissertations and Theses (Open Access)

After many years of cancer research, it is well accepted by the scientific community that the future cure for this disease lies in a personalized therapeutic approach. Anticipating therapeutic outcome based on the genetic signature of a tumor has become the new paradigm. The PI3K pathway represents an ideal target for bladder cancer, as many of the key proteins of this pathway are altered or mutated in this particular type of cancer. Several small molecule inhibitors have been developed to target this pathway, but their efficacy has been shown to be heterogeneous among different cell lines and mostly cytostatic but ...


Characterization Of Iron Response In Gynecological Cell Lines, Kyle A. Bauckman Mar 2014

Characterization Of Iron Response In Gynecological Cell Lines, Kyle A. Bauckman

Graduate Theses and Dissertations

Ovarian carcinoma afflicts over 22,000 women each year with a 5 year survival rate of only 18% for stage IV patients [23]. Current treatment options are limited due to high rates of drug resistance and recurrence. Further, the identity of "precursor lesions" which give rise to various subclasses of epithelial ovarian cancer has been evasive. This is due to discovery of the cancer at already an advanced stage. Interestingly, endometriosis a benign but invasive gynecological disease has been described as a "precursor lesion" in the development of specific subtypes of ovarian cancer. Endometriotic cyst development involves the accumulation of ...


Analysis Of The Role Of Two Autophagy Pathway Related Genes, Becn1 And Tsc1, In Murine Mammary Gland Development And Differentiation, Amber N. Hale Jan 2014

Analysis Of The Role Of Two Autophagy Pathway Related Genes, Becn1 And Tsc1, In Murine Mammary Gland Development And Differentiation, Amber N. Hale

Theses and Dissertations--Biology

The mammary gland is a dynamic organ that undergoes the majority of its development in the postnatal period in four stages; mature virgin, pregnancy, lactation, and involution. Every stage relies on tightly regulated cellular proliferation, programmed cell death, and tissue remodeling mechanisms. Misregulation of autophagy, an intracellular catabolic process to maintain energy stores, has long been associated with mammary tumorigenesis and other pathologies. We hypothesize that appropriate regulation and execution of autophagy are necessary for proper development of the mammary ductal tree and maintenance of the secretory epithelia during late pregnancy and lactation. To test this hypothesis we examined the ...


A Novel Autophagy Regulatory Mechanism That Functions During Programmed Cell Death: A Dissertation, Tsun-Kai Chang Sep 2013

A Novel Autophagy Regulatory Mechanism That Functions During Programmed Cell Death: A Dissertation, Tsun-Kai Chang

GSBS Dissertations and Theses

Autophagy is a cellular process that delivers cytoplasmic materials for degradation by the lysosomes. Autophagy-related (Atg) genes were identified in yeast genetic screens for vehicle formation under stress conditions, and Atg genes are conserved from yeast to human. When cells or animals are under stress, autophagy is induced and Atg8 (LC3 in mammal) is activated by E1 activating enzyme Atg7. Atg8-containing membranes form and surround cargos, close and mature to become the autophagosomes. Autophagosomes fuse with lysosomes, and cargos are degraded by lysosomal enzymes to sustain cell viability. Therefore, autophagy is most frequently considered to function in cell survival. Whether ...


Role Of Autophagy In Post-Mitotic Midbody Fate And Function: A Dissertation, Tse-Chun Kuo Mar 2013

Role Of Autophagy In Post-Mitotic Midbody Fate And Function: A Dissertation, Tse-Chun Kuo

GSBS Dissertations and Theses

The midbody (MB) is a proteinaceous complex formed between the two daughter cells during cell division and is required for the final cell separation event in late cytokinesis. After cell division, the post-mitotic midbody, or midbody derivative (MBd), can be retained and accumulated in a subpopulation of cancer cells and stem cells, but not in normal diploid differentiated cells. However, the mechanisms by which MBds accumulate and function are unclear. Based on this, I hypothesize that the MBd is degraded by autophagy after cell division in normal diploid differentiated cells, whereas non-differentiated cells have low autophagic ...


Drug Resistance Mechanisms To Gamma-Secretase Inhibitors In Human Colon Cancer Cells, Cindy R. Timme Jan 2013

Drug Resistance Mechanisms To Gamma-Secretase Inhibitors In Human Colon Cancer Cells, Cindy R. Timme

Graduate Theses and Dissertations

Colorectal cancer is the third leading cause of cancer-related mortality. Much progress has been achieved in combating this disease with surgical resection and chemotherapy in combination with targeted drugs. However, most metastatic patients develop drug resistance so new modalities of treatment are needed.

Notch signaling plays a vital role in intestinal homeostasis, self-renewal, and cell fate decisions during post-development and is activated in colorectal adenocarcinomas. Under debate is its role in carcinomas and metastatic disease. In theory, blocking Notch activation using gamma-secretase inhibitors (GSIs) may show efficacy alone or in combination with chemotherapy in the treatment of colon cancer.

In ...


The Interplay Between Lewy Body-Like Alpha-Synuclein Aggregates Nd Protein Degradation Pathways In Cell-Based Model Of Parkinson's Disease, Selcuk Aski Tanik Jan 2013

The Interplay Between Lewy Body-Like Alpha-Synuclein Aggregates Nd Protein Degradation Pathways In Cell-Based Model Of Parkinson's Disease, Selcuk Aski Tanik

Publicly Accessible Penn Dissertations

Cytoplasmic alpha-synuclein (a-syn) aggregates, including Lewy bodies (LBs), are pathological hallmarks of a number of neurodegenerative diseases, most notably Parkinson's disease (PD). Activation of intracellular protein degradation pathways (Pdps) to eliminate these aggregates has been proposed as a therapeutic approach for PD and other synucleinopathies, but the interplay between LB-like a-syn aggregates and Pdps is not completely understood. Here, we investigate this interplay by utilizing a recently developed cellular model in which intracellular LB-like a-syn inclusions accumulate after delivery of pre-formed a-syn fibrils (Pffs) into a-syn-expressing HEK293 cells or cultured primary neurons. This thesis describes the interplay between LB-like ...


Analysis Of The Function And The Regulation Of Autophagy In Arabidopsis Thaliana, Yimo Liu Jan 2012

Analysis Of The Function And The Regulation Of Autophagy In Arabidopsis Thaliana, Yimo Liu

Graduate Theses and Dissertations

Plants have developed sophisticated mechanisms to survive under adverse growth conditions. Autophagy is activated in response to multiple abiotic stresses, pathogen infection and senescence in plants. Upon induction of autophagy, portions of cytoplasm are engulfed by double membrane structures termed autophagosomes and are delivered to vacuole for degradation. Over the past decade, the identification of many autophagy-related genes in plants has greatly enhanced our molecular and physiological understanding of plant autophagy. However, the upstream regulatory components in the autophagy pathway and the function of autophagy under various stresses are still unclear. This thesis summarizes my efforts in studying the function ...


Mechanisms Of Adenovirus-Mediated Autophagy, Erin White Aug 2011

Mechanisms Of Adenovirus-Mediated Autophagy, Erin White

UT GSBS Dissertations and Theses (Open Access)

A patient diagnosed with a glioma, generally, has an average of 14 months year to live after implementation of conventional therapies such as surgery, chemotherapy, and radiation. Glioblastomas are highly lethal because of their aggressive nature and resistance to conventional therapies and apoptosis. Thus other avenues of cell death urgently need to be explored. Autophagy, which is also known as programmed cell death type II, has recently been identified as an alternative mechanism to kill apoptosis- resistant cancer cells. Traditionally, researchers have studied how cells undergo autophagy during viral infection as an immune response mechanism, but recently researchers have discovered ...


Atm Signaling To Tsc2: Mechanisms And Implications For Cancer Therapy, Angela Alexander May 2011

Atm Signaling To Tsc2: Mechanisms And Implications For Cancer Therapy, Angela Alexander

UT GSBS Dissertations and Theses (Open Access)

Ataxia telangiectasia mutated (ATM) is a critical component of the cellular response to DNA damage, where it acts as a damage sensor, and signals to a large network of proteins which execute the important tasks involved in responding to the damage, namely inducing cell cycle checkpoints, inducing DNA repair, modulating transcriptional responses, and regulating cell death pathways if the damage cannot be repaired faithfully. We have now discovered that an additional novel component of this ATM-dependent damage response involves induction of autophagy in response to oxidative stress. In contrast to DNA damage-induced ATM activation however, oxidative stress induced ATM, occurs ...


Molecular Mechanism Of Agc Kinases In Human Malignant, Shaokun Shu Oct 2010

Molecular Mechanism Of Agc Kinases In Human Malignant, Shaokun Shu

Graduate Theses and Dissertations

The maintenance of normal cell function and tissue homeostasis is dependent on the precise regulation of multiple signaling pathways that control cellular decisions to either proliferate, differentiate, arrest cell growth, or initiate programmed cell death (apoptosis). Cancer arises when clones of mutated cells escape this balance and proliferate inappropriately without compensatory apoptosis. Deregulated cell growth occurs as a result of perturbed signal transduction that modulates or alters cellular behavior or function to keep the critical balance between the rate of cell-cycle progression (cell division) and cell growth (cell mass) on one hand, and programmed cell death (apoptosis, autophagy) on the ...