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Autophagy

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Articles 31 - 44 of 44

Full-Text Articles in Cell Biology

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 ...


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 ...


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 ...


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 ...


Jnk Regulates Foxo-Dependent Autophagy In Neurons, Ping Xu, Madhumita Das, Judith Reilly, Roger J. Davis Feb 2011

Jnk Regulates Foxo-Dependent Autophagy In Neurons, Ping Xu, Madhumita Das, Judith Reilly, Roger J. Davis

Davis Lab Publications

The cJun N-terminal kinase (JNK) signal transduction pathway is implicated in the regulation of neuronal function. JNK is encoded by three genes that play partially redundant roles. Here we report the creation of mice with targeted ablation of all three Jnk genes in neurons. Compound JNK-deficient neurons are dependent on autophagy for survival. This autophagic response is caused by FoxO-induced expression of Bnip3 that displaces the autophagic effector Beclin-1 from inactive Bcl-XL complexes. These data identify JNK as a potent negative regulator of FoxO-dependent autophagy in neurons.


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 ...


Induction And Regulation Of Autophagy By Novel Prenylation Inhibitors In Sts-26t Malignant Peripheral Nerve Sheath Tumor (Mpnst) Cells, Komal Madhukar Sane Jan 2010

Induction And Regulation Of Autophagy By Novel Prenylation Inhibitors In Sts-26t Malignant Peripheral Nerve Sheath Tumor (Mpnst) Cells, Komal Madhukar Sane

Wayne State University Dissertations

Prenylation pathways have been targeted via several different compounds that inhibit farnesyl transferase (FTase) and/or geranylgeranyl transferase (GGTase) enzymes in many cellular and animal models of cancer. Some of these have also been evaluated in clinical trials with limited success. Multiple mechanisms of action have been elucidated for such compounds, including cell cycle arrest, proteasome inhibition, apoptosis and most recently, autophagy. However, there is still an urgent need of effective agents of this class of anti-tumor therapeutics. In this dissertation, I sought to delve into this issue by characterizing our novel prenylation inhibitors and their potential as anti-tumor agents ...