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 24 for “"TSC2"”.
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Atm Signaling to Tsc2: Mechanisms and Implications For Cancer Therapy
… to mTORC1 to induce autophagy via the LKB1-AMPK-TSC2 pathway. Targeting dysregulation of mTORC1 in <em>Atm</em>-deficient mice, which succumb to lymphomagenesis within 3-4 months of age with daily administration of rapamycin, could significantly extend survival and cause regression of tumors, …
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Mathematical Modeling Reveals That G2/M Checkpoint Override Creates A Therapeutic Vulnerability In Tsc2-Null Tumors
… pathway delayed G2/M checkpoint recovery, while TSC2-null cells with hyperactivity of mTORC1 exhibited the opposite results. Furthermore, our mechanistic study revealed that mTOR signaling pathway controls a transcriptional program of mitotic entry through regulating histone lysine demethylase …
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Mathematical Modeling Reveals That G2/M Checkpoint Override Creates A Therapeutic Vulnerability In Tsc2-Null Tumors
… pathway delayed G2/M checkpoint recovery, while TSC2-null cells with hyperactivity of mTORC1 exhibited the opposite results. Furthermore, our mechanistic study revealed that mTOR signaling pathway controls a transcriptional program of mitotic entry through regulating histone lysine demethylase …
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Therapeutic targeting of DGKA-mediated macropinocytosis in lymphangioleiomyomatosis
… by mutations in tumor suppressor genes TSC1 and TSC2. Spontaneous biallelic mutations in these genes can give rise to sporadic LAM. Mammalian target of rapamycin complex I (mTORC1), a master regulator of cellular anabolic metabolism is hyperactivated in LAM cells. Upregulation of protein …
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Biochemical and Biophysical Studies of Novel Features of Ras-related Protein Interactions
… The Tuberous Sclerosis Complex 2 protein (TSC2) regulates Rheb by functioning as a GTPase activating protein (GAP). At present, very little is known about the molecular features of the Rheb-TSC2 protein interaction. We present biochemical and biophysical data on the interaction of Rheb with …
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Characterization and Treatment of A Novel Mouse Model of Tsc-Associated Autism
… by mutations in either <em>TSC1 </em>or <em>TSC2.</em> The proteins of these genes form a complex to inhibit the mammalian target of rapamycin complex 1 (mTORC1), which controls protein translation and cell growth. TSC causes substantial neuropathology, often leading to autism spectrum …
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Molecular genetic investigation of the variability of the GTPase activating protein- (GAP-) related domain of the tuberous sclerosis-2 (TSC2) gene in TSC patients and healthy subjects
… 9q34.3 codes for the protein hamartin and TSC2 on chromosome 16p13.3 codes for tuberin. Tuberin shows homology to GTPase activating proteins (GAPs) and hamartin and tuberin may interact with one another to control the cell cycle, suggesting a tumor suppressor function for these proteins. …
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Characterizing and Treating The Neuropathology of Tuberous Sclerosis Complex In The Mouse
… mutations in either <em>TSC1</em> or <em>TSC2</em>, whose protein products are known inhibitors of mTORC1, an important kinase regulating translation and cell growth. Nonetheless, neither the pathophysiology of the neurological manifestations of TSC nor the extent of mTORC1 involvement in …
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Prevalence of Premature Ovarian Failure In Women With Tuberous Sclerosis
… mutations in either the <em>TSC1</em> or the <em>TSC2</em> gene cause most cases of TSC. Recently, the use of ovarian specific conditional knock-out mouse models has demonstrated a crucial role of the TSC genes in ovarian function. Mice with complete deletion of <em>Tsc1</em> or <em>Tsc2</em> …
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Mathematical Modeling Reveals That G2/M Checkpoint Override
… pathway delayed G2/M checkpoint recovery, while TSC2-null cells with hyperactivity of mTORC1 exhibited the opposite results. Furthermore, our mechanistic study revealed that mTOR signaling pathway controls a transcriptional program of mitotic entry through regulating histone lysine demethylase …
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Ankyrin-B and Mtor Complex 1 In The Regulation of Electrical Activities In The Heart
… In the brain, the tumor suppressor gene <em>TSC2</em> encodes the protein product tuberin that interacts with hamartin to form a heterodimer Tuberous Sclerosis Complex (TSC) that regulates mTORC1. When <em>TSC2 </em>is disrupted, mTORC1 activity becomes dysregulated resulting in abnormal …
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The identification of the mTOR-regulated phosphoproteome and a mediator of feedback inhibition to P13K-Akt
… the inhibition of P13K typical of cells lacking TSC2, a tumor suppressor and negative regulator of mTORC1. Phosphorylation of Grbl 0 is important for its inhibitory function as well as for its stability. While acute mTORC1 inhibition results in changes in Grb1O and IRS1 phosphorylation which …
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The PI3-Kinase/TSC Pathway: A Role in Neural and Renal Development and Pathology
… TSC1/2 complex by directly phosphorylating TSC2, and in turn releases the inhibition of TSC1/2 complex on mTOR. Thus, loss of either PTEN or TSC1 or TSC2 can result in increased mTOR activity. However, regulation of TSC1/2 complex by AKT could be context dependent and the TSC/mTOR pathway is …
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Mtorc1 Signaling In Memory Formation and Dysfunction
… of mTORC1 would improve outcome. Using a TSC2 knock-out mouse model we investigated the effects of elevated mTORC1 activity on outcome using hippocampal-dependent learning and memory tasks. My results suggest that acute overactivation of mTORC1 impairs long-term memory after brain injury …
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Developing Fluorescent Tools to Dissect the Role of Tuberin at Mitotic Onset
… by inactivating mutations in either the TSC1 or TSC2 gene encoding for Hamartin and Tuberin, respectively. Mechanistically, Hamartin and Tuberin form a tumour suppressor complex by negatively regulating the mTORC1 pathway and inhibiting protein synthesis. Our lab has characterized how Tuberin …
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AMP-activated protein kinase-mTOR signaling pathway and hepatitis B virus replication
… protein of mTOR(Raptor)와 tuberous sclerosis 2(TSC2)의 인산화는 증가하였다. HepG2.2.15세포에서 Akt 발현과 인산화가 증가하였다. Protein phosphatase 2A(PP2A), S6 kinase 1(S6K1)와 eukaryotic translation initiation factor 4E-binding protein 1(4E-BP1)의 발현과 인산화는 HepG2.2.15세포에서 증가하였다. Huh7 HBV WT stable 세포에서는 S6K1의 인산화, PP2A의 …
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Examination of type I IFN mediated regulation of the post-transcriptional antiviral response
… that cells lacking suppressors of translation, TSC2 or 4E-BP1, are more sensitive to IFN-α/β inducible effects as indicated by increased antiviral protein synthesis, and enhanced resistance to virus infection. In vivo experiments showed that mice lacking 4E-BP1 are similarly more resistant to …
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Regulation of peripheral nerve regeneration by the mTOR pathway
… by deletion of tuberous sclerosis complex 2: TSC2) in DRGs is sufficient to enhance axonal growth capacity in vitro and in vivo. We identified GAP-43 as a downstream target of this pathway, which may contribute to enhance regenerative ability. However, while genetic upregulation of mTOR …
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Signal Transduction in Skeletal Muscle Mediating Responses to Phenotype Altering Signals
… no effect on PICB phosphorylation but reduced TSC2 phosphorylation at Thr1462 and deactivated translational regulators. In contrast, HFS acutely increased phosphorylation of PKB at Ser473 5.3-fold and the phosphorylation of TSC2, mTOR, GSK-3j3 at PKB-sensitive sites. HFS also caused a prolonged …
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THE ROLE OF TRANSLATION ELONGATION DEFICITS IN ALZHEIMER’S DISEASE PATHOGENESIS
… the gene for tuberous sclerosis complex 2 (TSC2+/-), an upstream negative regulator of eEF1A, we upregulated eEF1A expression and prevented Aβ-induced synaptic plasticity deficits. Unlike eEF1A, expression of eEF2 was not altered in hippocampal samples from human AD patients. Instead, eEF2 …
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