The Experts below are selected from a list of 377355 Experts worldwide ranked by ideXlab platform
Petrus J De Vries - One of the best experts on this subject based on the ideXlab platform.
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evolution of the tsc1 tsc2 tor Signaling Pathway
Science Signaling, 2010Co-Authors: Jaco Serfontein, Ellen R R Nisbet, Christopher J. Howe, Petrus J De VriesAbstract:The TSC1/TSC2-TOR Signaling Pathway [the Signaling Pathway that includes the heterodimeric TSC1 (tuberous sclerosis 1 protein)–TSC2 (tuberous sclerosis 2 protein) complex and TOR (target of rapamycin)] regulates various cellular processes, including protein synthesis, in response to growth factors and nutrient availability. Homologs of some Pathway components have been reported from animals, fungi, plants, and protozoa. These observations led to the perception that the whole Pathway is evolutionarily conserved throughout eukaryotes. Using complete genome sequences, we show that, contrary to this view, the Pathway was built up from a simpler one, present in the ancestral eukaryote, coupling cell growth to energy supplies. Additional elements, such as TSC1 and TSC2, were “bolted on” in particular eukaryotic lineages. Our results also suggest that unikonts [Opisthokonta (including animals and fungi) and Amoebozoa] form a monophyletic group with the Excavata and Chromalveolata. A previous proposal, that the root of the eukaryotic “tree of life” lies between the unikonts and other organisms, should therefore be reevaluated.
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Evolution of the TSC1/TSC2-TOR Signaling Pathway
Science Signaling, 2010Co-Authors: Jaco Serfontein, R. Ellen R. Nisbet, Christopher J. Howe, Petrus J De VriesAbstract:The TSC1/TSC2-TOR Signaling Pathway [the Signaling Pathway that includes the heterodimeric TSC1 (tuberous sclerosis 1 protein)-TSC2 (tuberous sclerosis 2 protein) complex and TOR (target of rapamycin)] regulates various cellular processes, including protein synthesis, in response to growth factors and nutrient availability. Homologs of some Pathway components have been reported from animals, fungi, plants, and protozoa. These observations led to the perception that the whole Pathway is evolutionarily conserved throughout eukaryotes. Using complete genome sequences, we show that, contrary to this view, the Pathway was built up from a simpler one, present in the ancestral eukaryote, coupling cell growth to energy supplies. Additional elements, such as TSC1 and TSC2, were "bolted on" in particular eukaryotic lineages. Our results also suggest that unikonts [Opisthokonta (including animals and fungi) and Amoebozoa] form a monophyletic group with the Excavata and Chromalveolata. A previous proposal, that the root of the eukaryotic "tree of life" lies between the unikonts and other organisms, should therefore be reevaluated.
Jaco Serfontein - One of the best experts on this subject based on the ideXlab platform.
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evolution of the tsc1 tsc2 tor Signaling Pathway
Science Signaling, 2010Co-Authors: Jaco Serfontein, Ellen R R Nisbet, Christopher J. Howe, Petrus J De VriesAbstract:The TSC1/TSC2-TOR Signaling Pathway [the Signaling Pathway that includes the heterodimeric TSC1 (tuberous sclerosis 1 protein)–TSC2 (tuberous sclerosis 2 protein) complex and TOR (target of rapamycin)] regulates various cellular processes, including protein synthesis, in response to growth factors and nutrient availability. Homologs of some Pathway components have been reported from animals, fungi, plants, and protozoa. These observations led to the perception that the whole Pathway is evolutionarily conserved throughout eukaryotes. Using complete genome sequences, we show that, contrary to this view, the Pathway was built up from a simpler one, present in the ancestral eukaryote, coupling cell growth to energy supplies. Additional elements, such as TSC1 and TSC2, were “bolted on” in particular eukaryotic lineages. Our results also suggest that unikonts [Opisthokonta (including animals and fungi) and Amoebozoa] form a monophyletic group with the Excavata and Chromalveolata. A previous proposal, that the root of the eukaryotic “tree of life” lies between the unikonts and other organisms, should therefore be reevaluated.
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Evolution of the TSC1/TSC2-TOR Signaling Pathway
Science Signaling, 2010Co-Authors: Jaco Serfontein, R. Ellen R. Nisbet, Christopher J. Howe, Petrus J De VriesAbstract:The TSC1/TSC2-TOR Signaling Pathway [the Signaling Pathway that includes the heterodimeric TSC1 (tuberous sclerosis 1 protein)-TSC2 (tuberous sclerosis 2 protein) complex and TOR (target of rapamycin)] regulates various cellular processes, including protein synthesis, in response to growth factors and nutrient availability. Homologs of some Pathway components have been reported from animals, fungi, plants, and protozoa. These observations led to the perception that the whole Pathway is evolutionarily conserved throughout eukaryotes. Using complete genome sequences, we show that, contrary to this view, the Pathway was built up from a simpler one, present in the ancestral eukaryote, coupling cell growth to energy supplies. Additional elements, such as TSC1 and TSC2, were "bolted on" in particular eukaryotic lineages. Our results also suggest that unikonts [Opisthokonta (including animals and fungi) and Amoebozoa] form a monophyletic group with the Excavata and Chromalveolata. A previous proposal, that the root of the eukaryotic "tree of life" lies between the unikonts and other organisms, should therefore be reevaluated.
Jeffrey S Rubin - One of the best experts on this subject based on the ideXlab platform.
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Existence of the canonical Wnt Signaling Pathway in the human trabecular meshwork.
Investigative Ophthalmology & Visual Science, 2012Co-Authors: Weiming Mao, Wanheng Wang, Sean Silverman, Robert J Wordinger, Jeffrey S Rubin, Iokhou Pang, J. Cameron Millar, Yang Liu, F. ClarkAbstract:Purpose We previously discovered elevated levels of secreted frizzled-related protein 1 (sFRP1), the Wnt Signaling Pathway inhibitor, in the glaucomatous trabecular meshwork (GTM), and found that key canonical Wnt Signaling Pathway genes are expressed in the trabecular meshwork (TM). The purpose of our study was to determine whether a functional canonical Wnt Signaling Pathway exists in the human TM (HTM). Methods Western immunoblotting and/or immunofluorescent microscopy were used to study β-catenin translocation as well as the actin cytoskeleton in transformed and primary HTM cells. A TCF/LEF luciferase assay was used to study functional canonical Wnt Signaling, which was confirmed further by WNT3a-induced expression of a Pathway target gene, AXIN2, via quantitative PCR. Intravitreal injection of an Ad5 adenovirus expressing Dickkopf-related protein-1 (DKK1) was used to study the in vivo effect of canonical Wnt Signaling on IOP in mice. Results WNT3a induced β-catenin translocation in the HTM, which was blocked by co-treatment with sFRP1. Similarly, WNT3a enhanced luciferase levels in TCF/LEF luciferase assays, which also were blocked by sFRP1. Furthermore, AXIN2 expression was elevated significantly by WNT3a. However, neither WNT3a nor sFRP1 affected actin cytoskeleton organization, which theoretically could be regulated by noncanonical Wnt Signaling in HTM cells. Exogenous DKK1, a specific inhibitor for the canonical Wnt Signaling Pathway, or sFRP1 elevated mouse IOP to equivalent levels. Conclusions There is a canonical Wnt Signaling Pathway in the TM, and this canonical Wnt Pathway, but not the noncanonical Wnt Signaling Pathway, regulates IOP.
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existence of the canonical wnt Signaling Pathway in the human trabecular meshwork
Investigative Ophthalmology & Visual Science, 2012Co-Authors: Cameron J Millar, Wanheng Wang, Sean Silverman, Robert J Wordinger, Jeffrey S Rubin, Iokhou Pang, Abbot F ClarkAbstract:We previously discovered elevated levels of secreted frizzled-related protein 1 (sFRP1), the Wnt Signaling Pathway inhibitor, in the glaucomatous trabecular meshwork (GTM), and found that key canonical Wnt Signaling Pathway genes are expressed in the trabecular meshwork (TM). The purpose of our study was to determine whether a functional canonical Wnt Signaling Pathway exists in the human TM (HTM).Western immunoblotting and/or immunofluorescent microscopy were used to study β-catenin translocation as well as the actin cytoskeleton in transformed and primary HTM cells. A TCF/LEF luciferase assay was used to study functional canonical Wnt Signaling, which was confirmed further by WNT3a-induced expression of a Pathway target gene, AXIN2, via quantitative PCR. Intravitreal injection of an Ad5 adenovirus expressing Dickkopf-related protein-1 (DKK1) was used to study the in vivo effect of canonical Wnt Signaling on IOP in mice.WNT3a induced β-catenin translocation in the HTM, which was blocked by co-treatment with sFRP1. Similarly, WNT3a enhanced luciferase levels in TCF/LEF luciferase assays, which also were blocked by sFRP1. Furthermore, AXIN2 expression was elevated significantly by WNT3a. However, neither WNT3a nor sFRP1 affected actin cytoskeleton organization, which theoretically could be regulated by noncanonical Wnt Signaling in HTM cells. Exogenous DKK1, a specific inhibitor for the canonical Wnt Signaling Pathway, or sFRP1 elevated mouse IOP to equivalent levels.There is a canonical Wnt Signaling Pathway in the TM, and this canonical Wnt Pathway, but not the noncanonical Wnt Signaling Pathway, regulates IOP.
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akt participation in the wnt Signaling Pathway through dishevelled
Journal of Biological Chemistry, 2001Co-Authors: Shinya Fukumoto, Chungming Hsieh, Koji Maemura, Matthew D Layne, Shawfang Yet, Kyunghan Lee, Takashi Matsui, Anthony Rosenzweig, William G Taylor, Jeffrey S RubinAbstract:Abstract Inactivation of glycogen synthase kinase 3β (GSK3β) and the resulting stabilization of free β-catenin are critical steps in the activation of Wnt target genes. While Akt regulates GSK3α/β in the phosphatidylinositide 3-OH kinase Signaling Pathway, its role in Wnt Signaling is unknown. Here we report that expression of Wnt or Dishevelled (Dvl) increased Akt activity. Activated Akt bound to the Axin-GSK3β complex in the presence of Dvl, phosphorylated GSK3β and increased free β-catenin levels. Furthermore, in Wnt-overexpressing PC12 cells, dominant-negative Akt decreased free β-catenin and derepressed nerve growth factor-induced differentiation. Therefore, Akt acts in association with Dvl as an important regulator of the Wnt Signaling Pathway.
Christopher J. Howe - One of the best experts on this subject based on the ideXlab platform.
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evolution of the tsc1 tsc2 tor Signaling Pathway
Science Signaling, 2010Co-Authors: Jaco Serfontein, Ellen R R Nisbet, Christopher J. Howe, Petrus J De VriesAbstract:The TSC1/TSC2-TOR Signaling Pathway [the Signaling Pathway that includes the heterodimeric TSC1 (tuberous sclerosis 1 protein)–TSC2 (tuberous sclerosis 2 protein) complex and TOR (target of rapamycin)] regulates various cellular processes, including protein synthesis, in response to growth factors and nutrient availability. Homologs of some Pathway components have been reported from animals, fungi, plants, and protozoa. These observations led to the perception that the whole Pathway is evolutionarily conserved throughout eukaryotes. Using complete genome sequences, we show that, contrary to this view, the Pathway was built up from a simpler one, present in the ancestral eukaryote, coupling cell growth to energy supplies. Additional elements, such as TSC1 and TSC2, were “bolted on” in particular eukaryotic lineages. Our results also suggest that unikonts [Opisthokonta (including animals and fungi) and Amoebozoa] form a monophyletic group with the Excavata and Chromalveolata. A previous proposal, that the root of the eukaryotic “tree of life” lies between the unikonts and other organisms, should therefore be reevaluated.
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Evolution of the TSC1/TSC2-TOR Signaling Pathway
Science Signaling, 2010Co-Authors: Jaco Serfontein, R. Ellen R. Nisbet, Christopher J. Howe, Petrus J De VriesAbstract:The TSC1/TSC2-TOR Signaling Pathway [the Signaling Pathway that includes the heterodimeric TSC1 (tuberous sclerosis 1 protein)-TSC2 (tuberous sclerosis 2 protein) complex and TOR (target of rapamycin)] regulates various cellular processes, including protein synthesis, in response to growth factors and nutrient availability. Homologs of some Pathway components have been reported from animals, fungi, plants, and protozoa. These observations led to the perception that the whole Pathway is evolutionarily conserved throughout eukaryotes. Using complete genome sequences, we show that, contrary to this view, the Pathway was built up from a simpler one, present in the ancestral eukaryote, coupling cell growth to energy supplies. Additional elements, such as TSC1 and TSC2, were "bolted on" in particular eukaryotic lineages. Our results also suggest that unikonts [Opisthokonta (including animals and fungi) and Amoebozoa] form a monophyletic group with the Excavata and Chromalveolata. A previous proposal, that the root of the eukaryotic "tree of life" lies between the unikonts and other organisms, should therefore be reevaluated.
Fazlul H Sarkar - One of the best experts on this subject based on the ideXlab platform.
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regulation of emt by notch Signaling Pathway in tumor progression
Current Cancer Drug Targets, 2013Co-Authors: Xiujuan Qian, Jun Xia, Lucio Miele, Fazlul H Sarkar, Zhiwei WangAbstract:Notch Signaling Pathway has been reported to play critical roles in the development and progression of human cancers because Notch Signaling Pathway is critically involved in many cellular processes including cell proliferation, survival, apoptosis, migration, invasion, angiogenesis, and metastasis. Emerging evidence suggests that Notch regulates EMT (Epithelial-to-Mesenchymal Transition), leading to tumor invasion and metastasis. Thus, this mini-review is focused on discussing the novel role of Notch Signaling Pathway in the regulation of EMT. Moreover, we summarized that Notch Signaling Pathway could be down-regulated by its inhibitors or natural compounds, resulting in the reversal of EMT to MET (Mesenchymal-to-Epithelial Transition), which could be a promising strategy for achieving better treatment outcome in patients diagnosed with cancer.
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targeting the hedgehog Signaling Pathway for cancer therapy
Expert Opinion on Therapeutic Targets, 2012Co-Authors: Main Y Maitah, Dejuan Kong, Aamir Ahmad, Bin Bao, Fazlul H SarkarAbstract:Introduction: Hedgehog (Hh) Signaling Pathway plays key roles in embryonic development, formation and maintenance of cancer stem cells (CSCs) and acquisition of epithelial-to-mesenchymal transition (EMT). Since CSCs and EMT are important biological factors responsible for cancer cell invasion, metastasis, drug resistance and tumor recurrence, the Hh Signaling Pathway is believed to be an important target for cancer therapy. Areas covered: In recent years, small-molecule inhibitors of Hh Signaling have been synthesized for cancer treatment. Clinical trials using these inhibitors are being conducted to determine their toxicity profiles and efficacies. In addition, nutraceuticals (such as isoflavones, curcumin, vitamin D, etc) have been shown to inhibit cancer growth through downregulation of Hh Signaling. Expert opinion: Inhibition of Hh Signaling is important for suppression of cancer growth, invasion, metastasis and recurrence in cancer therapy. However, targeting only one molecule in Hh Signaling may not...
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the role of notch Signaling Pathway in epithelial mesenchymal transition emt during development and tumor aggressiveness
Current Drug Targets, 2010Co-Authors: Zhiwei Wang, Dejuan Kong, Fazlul H SarkarAbstract:The Notch Signaling Pathway maintains a balance between cell proliferation and apoptosis, and thus it is believed that Notch Signaling Pathway may play an important role in the development and progression of several malignancies. However, the functions of Notch Signaling in EMT are largely unknown. This mini review describes the role of Notch Signaling Pathway in EMT, and cataloging how its deregulation is involved in EMT and tumor aggressiveness. Further attempts have been made to summarize the role of several chemopreventive agents that could be useful for targeted inactivation of Notch Signaling, and thus it may cause reversal of EMT, which could become a novel approach for cancer prevention and treatment.
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exploitation of the notch Signaling Pathway as a novel target for cancer therapy
Anticancer Research, 2008Co-Authors: Zhiwei Wang, Sanjeev Banerjee, Fazlul H SarkarAbstract:The Notch Signaling Pathway appears to be responsible for maintaining a balance between cell proliferation and apoptosis and thus it has been suggested that Notch may play an important role in species development and in the development and progression of several malignancies. Therefore, the Notch Signaling Pathway may represent a novel therapeutic target, which could have the highest therapeutic impact in modern medicine. This review describes the mechanisms of signal transduction of the Notch Signaling Pathway and provides emerging evidence in support of its role in the development of human malignancies. Further attempts have been made to summarize the role of several chemopreventive agents that could be useful for targeted inactivation of Notch Signaling, which could become a novel approach for cancer prevention and treatment.
