Global ETD Search
Search theses and dissertations gathered from participating repositories worldwide. Every result links back to the library that holds it. No account is needed.
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Showing 1 to 20 of 31 for “"mTORC1 signaling"”.
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The localization of mTORC1 signaling
… activity levels and localizations of key signaling proteins. In eukaryotic cells, cell size is increasingly appreciated as being coordinated by the Target of Rapamycin (TOR) Pathway. TOR is a serine/threonine kinase that resides in two distinct protein complexes which in mammals are …
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Mtorc1 Signaling In Memory Formation and Dysfunction
<p>The mechanistic Target of Rapamycin Complex 1 (mTORC1) pathway integrates cellular availability of growth factors, energy and amino acids to regulate protein synthesis and autophagy. The mTORC1 pathway has also been shown to be required for memory consolidation, and its dysregulation is …
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TRPML1 Promotes Protein Homeostasis in Melanoma Cells by Negatively Regulating MAPK and mTORC1 Signaling
… cells to negatively regulate MAPK pathway and mTORC1 signaling. TRPML1-deficient melanoma cells exhibited decreased survival, proliferation, tumor growth, and macropinocytosis as well as serine depletion and proteotoxic stress. All of these phenotypes were partially or completely rescued by …
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Identification of Molecular Targets for the Treatment of the Skeletal Phenotype in Lysosomal Storage Disorders
… is essential for tissue homeostasis. The mTORC1 kinase tunes autophagy according to nutrient levels and environmental factors. Recently the laboratory in which I performed the experiments used for my thesis has demonstrated that autophagy, by controlling collagen secretion in chondrocytes, …
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Intramuscular Anabolic Signaling and Endocrine Response Following Different Resistance Exercise Protocols In Trained Men
… target of rapamycin complex 1 (mTORC1) signaling pathway appears to be the primary regulator of protein synthesis and growth. While resistance exercise paradigms are often divided into hypertrophy (HYP) and strength (STR) protocols, it is unknown whether these protocols …
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Involvement of Gdap1 In The Regulation of Mtorc1 Activity In A Drosophila Mliv Model
… mechanistic target of rapamycin complex 1 (mTORC1), is responsible for maintaining metabolic homeostasis by sensing nutrient and energy levels within the cell to promote or inhibit translation and autophagy accordingly. In the childhood neurodevelopmental disorder Mucolipidosis type IV …
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MODULATING TFEB ACTIVITY IN THE BIRT-HOGG-DUBE' SYNDROME BY TARGETING THE VACUOLAR ATPASE
… is primarily controlled by the kinase complex mTORC1. In the Birt-Hogg-Dubé (BHD) syndrome, a genetic disease caused by germline mutations in FLCN gene, TFEB was found to be constitutively active and to promote the development of kidney cysts and cancer. Therefore, inhibition of TFEB activity …
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Molecular Mechanisms Underlying Innate Immune Kinase TBK1-Driven Oncogenic Transformation
An essential kinase in innate immune signaling, TBK1 couples pathogen surveillance to induction of host defense mechanisms. The pathological activation of TBK1 in cancer can overcome programmed cell death cues, enabling cells to survive oncogenic stress. The mechanistic basis of TBK1 prosurvival …
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The Effect of Cancer Cachexia Progression on the Feeding Regulation of Skeletal Muscle Protein Turnover
… and systemic stimuli that are controlled by mTORC1 and AMPK signaling. During cachexia, altered protein turnover is thought to occur through suppressed anabolic signaling via mTORC1, coinciding with the chronic activation of AMPK. While progress has been made in understanding some of the …
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Integration of amino acid signals by the mTORC1 pathway
… The mechanistic target of rapamycin complex 1 (mTORC1) kinase pathway is the primary eukaryotic pathway responsible for integrating these diverse signals and coordinating cell growth programs. When activated by environmental cues that favors cell and organismal growth, mTORC1 phosphorylates …
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Biochemical and physiological exploration of the nutrient sensing pathway upstream of mTORC1
The mTORC1 (mechanistic target of rapamycin complex 1) protein kinase controls growth in response to environmental cues. Aberrant mTORC1 activity is linked to numerous diseases including cancer. Understanding the regulation of mTORC1 will facilitate therapeutic developments. Amino acids promote the …
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Differential BCAA Metabolism in Tissues of Tumor-Bearing Mice: A Path to Understanding Cancer Cachexia
… of mechanistic target of rapamycin complex 1 (mTORC1) signaling. Notably, the soleus muscle maintained mTORC1 activity despite reduced BCAA availability, suggesting fiber-type–specific adaptations. These findings indicate that tumors act as metabolic sinks, diverting systemic amino acids away …
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A systematic approach for cataloging mTORC1 regulators
mTORC1 is a major regulator of eukaryotic cell growth. As a cellular decision-maker, mTORC1 surveils internal levels of basic biomolecules such as amino acids, ATP, cholesterol, and external levels of growth factors. Under sufficient nutrient conditions, mTORC1 is active and drives anabolic …
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Unraveling Molecular Mechanisms Underlying the Development of Unconventional T Cells
… deletion of RAPTOR, we found RAPTOR-dependent mTORC1 signaling couples microenvironmental cues with metabolic programs to orchestrate the reciprocal development of two fundamentally distinct T cell lineages: αβ and γδ-T cells. Loss of RAPTOR impaired αβ but promoted γδ-T cell development while …
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Generation of focal Depdc5 knockout mouse model and implications for focal epilepsy
… defects or later neuronal dysfunction of mTORC1 signaling. To test this, we developed a postnatal adeno-associated virus (AAV) mediated focal cortical Depdc5 knockout mouse model. Viral vectors containing either 2/8AAV-Cre or control 2/8AAV-GFP were injected into the unilateral motor …
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Mathematical Modeling Reveals That G2/M Checkpoint Override
… impacts on cell fate. In tumor cells, the signaling network has been rewired due to epigenetic and genetic alterations, which result in resistance to the cell cycle control, and thus resistance to chemotherapy or radiation therapy. Therefore, it is critical to identify molecules required …
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Mathematical Modeling Reveals That G2/M Checkpoint Override Creates A Therapeutic Vulnerability In Tsc2-Null Tumors
… impacts on cell fate. In tumor cells, the signaling network has been rewired due to epigenetic and genetic alterations, which result in resistance to the cell cycle control, and thus resistance to chemotherapy or radiation therapy. Therefore, it is critical to identify molecules required …
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Mathematical Modeling Reveals That G2/M Checkpoint Override Creates A Therapeutic Vulnerability In Tsc2-Null Tumors
… impacts on cell fate. In tumor cells, the signaling network has been rewired due to epigenetic and genetic alterations, which result in resistance to the cell cycle control, and thus resistance to chemotherapy or radiation therapy. Therefore, it is critical to identify molecules required …
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Identifying a role for the scaffolding protein IQGAP1 in liver health and disease
… with impaired PPARα activation and hyperactive mTORC1 signaling. Furthermore, in chapter 4 I show that IQGAP1 is upregulated at a transcriptional level by bile acid signaling and its deletion results in increased toxin-induced liver injury and bile acid accumulation. E-cadherin, which is …
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Regulation of the mTORC1 growth pathway by amino acids
The mTORC1 kinase is a master growth regulator that responds to numerous environmental cues, including amino acids, to regulate many processes, such as protein, lipid, and nucleotide synthesis, as well as autophagy. Given that mTORC1 regulates a multitude of processes, it is not surprising that the …
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