The Experts below are selected from a list of 61926 Experts worldwide ranked by ideXlab platform
Laura R Lee - One of the best experts on this subject based on the ideXlab platform.
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the ino80 chromatin remodeler sustains metabolic stability by promoting tor signaling and regulating histone acetylation
PLOS Genetics, 2018Co-Authors: Sean L Beckwith, Erin K Schwartz, Pablo E Garcianieto, Devin A King, Graeme J Gowans, Ka Man Wong, Tessa L Eckley, Alexander P Paraschuk, Egan L Peltan, Laura R LeeAbstract:Chromatin remodeling complexes are essential for gene expression programs that coordinate cell function with metabolic status. However, how these remodelers are integrated in metabolic stability pathways is not well known. Here, we report an expansive genetic screen with chromatin remodelers and metabolic regulators in Saccharomyces cerevisiae. We found that, unlike the SWR1 remodeler, the INO80 chromatin remodeling complex is composed of multiple distinct Functional Subunit modules. We identified a strikingly divergent genetic signature for the Ies6 Subunit module that links the INO80 complex to metabolic homeostasis. In particular, mitochondrial maintenance is disrupted in ies6 mutants. INO80 is also needed to communicate TORC1-mediated signaling to chromatin, as ino80 mutants exhibit defective transcriptional profiles and altered histone acetylation of TORC1-responsive genes. Furthermore, comparative analysis reveals Subunits of INO80 and mTORC1 have high co-occurrence of alterations in human cancers. Collectively, these results demonstrate that the INO80 complex is a central component of metabolic homeostasis that influences histone acetylation and may contribute to disease when disrupted.
Paul Schaffer - One of the best experts on this subject based on the ideXlab platform.
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non invasive use of positron emission tomography to monitor diethyl maleate and radiation induced changes in system x c activity in breast cancer
Molecular Imaging and Biology, 2019Co-Authors: Milena Colovic, Hua Yang, Helen Merkens, Nadine Colpo, Francois Benard, Paul SchafferAbstract:The system xC− transporter is upregulated in cancer cells in response to oxidative stress (OS). 5-[18F]fluoroaminosuberic acid ([18F]FASu) has been reported as a novel positron emission tomography (PET) imaging agent, targeting system xC−. The goal of this study was to evaluate the utility of [18F]FASu in monitoring cellular response to diethyl maleate (DEM) and radiation-induced OS fluctuations. [18F]FASu uptake by breast cancer cells was studied in correlation to OS biomarkers: glutathione (GSH) and reactive oxygen species (ROS), as well as transcriptional and translational levels of xCT (the Functional Subunit of xC−). System xC− inhibitor, sulfasalazine (SSZ), and small interfering RNA (siRNA) knockdown were used as negative controls. Radiotracer uptake was evaluated in three breast cancer models: MDA-MB-231, MCF-7, and ZR-75-1, at two-time points (1 h and 16 h) following OS induction. In vivo [18F]FASu imaging and biodistribution were performed using MDA-MB-231 xenograft-bearing mice at 16 and 24 h post-radiation treatment. [18F]FASu uptake was positively correlated to intracellular GSH and SLC7A11 expression levels, and radiotracer uptake was induced both by radiation treatment and by DEM at time points longer than 3 h. In an in vivo setting, there was no statistically significant uptake difference between irradiated and control tumors. [18F]FASu is a specific system xC− PET radiotracer and as such it can be used to monitor system xC− activity due to OS. As such, [18F]FASu has the potential to be used in therapy response monitoring by PET. Further optimization is required for in vivo application.
Douglas Yee - One of the best experts on this subject based on the ideXlab platform.
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igf i regulates redox status in breast cancer cells by activating the amino acid transport molecule xc
Cancer Research, 2014Co-Authors: Yuzhe Yang, Douglas YeeAbstract:Insulin-like growth factors (IGF) stimulate cell growth in part by increasing amino acid uptake. xCT (SLC7A11) encodes the Functional Subunit of the cell surface transport system xC(-), which mediates cystine uptake, a pivotal step in glutathione synthesis and cellular redox control. In this study, we show that IGF-I regulates cystine uptake and cellular redox status by activating the expression and function of xCT in estrogen receptor-positive (ER(+)) breast cancer cells by a mechanism that relies on the IGF receptor substrate-1 (IRS-1). Breast cancer cell proliferation mediated by IGF-I was suppressed by attenuating xCT expression or blocking xCT activity with the pharmacologic inhibitor sulfasalazine (SASP). Notably, SASP sensitized breast cancer cells to inhibitors of the type I IGF receptor (IGF-IR) in a manner reversed by the reactive oxygen species (ROS) scavenger N-acetyl-L-cysteine. Thus, IGF-I promoted the proliferation of ER(+) breast cancer cells by regulating xC(-) transporter function to protect cancer cells from ROS in an IRS-1-dependent manner. Our findings suggest that inhibiting xC(-) transporter function may synergize with modalities that target the IGF-IR to heighten their therapeutic effects.
Sean L Beckwith - One of the best experts on this subject based on the ideXlab platform.
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the ino80 chromatin remodeler sustains metabolic stability by promoting tor signaling and regulating histone acetylation
PLOS Genetics, 2018Co-Authors: Sean L Beckwith, Erin K Schwartz, Pablo E Garcianieto, Devin A King, Graeme J Gowans, Ka Man Wong, Tessa L Eckley, Alexander P Paraschuk, Egan L Peltan, Laura R LeeAbstract:Chromatin remodeling complexes are essential for gene expression programs that coordinate cell function with metabolic status. However, how these remodelers are integrated in metabolic stability pathways is not well known. Here, we report an expansive genetic screen with chromatin remodelers and metabolic regulators in Saccharomyces cerevisiae. We found that, unlike the SWR1 remodeler, the INO80 chromatin remodeling complex is composed of multiple distinct Functional Subunit modules. We identified a strikingly divergent genetic signature for the Ies6 Subunit module that links the INO80 complex to metabolic homeostasis. In particular, mitochondrial maintenance is disrupted in ies6 mutants. INO80 is also needed to communicate TORC1-mediated signaling to chromatin, as ino80 mutants exhibit defective transcriptional profiles and altered histone acetylation of TORC1-responsive genes. Furthermore, comparative analysis reveals Subunits of INO80 and mTORC1 have high co-occurrence of alterations in human cancers. Collectively, these results demonstrate that the INO80 complex is a central component of metabolic homeostasis that influences histone acetylation and may contribute to disease when disrupted.
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the ino80 chromatin remodeler sustains metabolic stability by promoting tor signaling and regulating histone acetylation
bioRxiv, 2017Co-Authors: Sean L Beckwith, Erin K Schwartz, Pablo E Garcianieto, Devin A King, Graeme J Gowans, Ka Man Wong, Wei Yao, Tessa L Eckley, Alexander P Paraschuk, Egan L PeltanAbstract:Chromatin remodeling complexes are essential for gene expression programs that coordinate cell function with metabolic status. However, how these remodelers are integrated in metabolic stability pathways is not well known. Here, we report an expansive genetic screen with chromatin remodelers and metabolic regulators in Saccharomyces cerevisiae. We found that, unlike the SWR1 remodeler, the INO80 chromatin remodeling complex is composed of multiple distinct Functional Subunit modules. We identified a strikingly divergent genetic signature for the Ies6 Subunit module that links the INO80 complex to metabolic homeostasis, including mitochondrial maintenance. INO80 is also needed to communicate TORC1-mediated signaling to chromatin and maintains histone acetylation at TORC1-responsive genes. Furthermore, computational analysis reveals Subunits of INO80 and mTORC1 have high co-occurrence of alterations in human cancers. Collectively, these results demonstrate that the INO80 complex is a central component of metabolic homeostasis that influences histone acetylation and may contribute to disease when disrupted.
Egan L Peltan - One of the best experts on this subject based on the ideXlab platform.
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the ino80 chromatin remodeler sustains metabolic stability by promoting tor signaling and regulating histone acetylation
PLOS Genetics, 2018Co-Authors: Sean L Beckwith, Erin K Schwartz, Pablo E Garcianieto, Devin A King, Graeme J Gowans, Ka Man Wong, Tessa L Eckley, Alexander P Paraschuk, Egan L Peltan, Laura R LeeAbstract:Chromatin remodeling complexes are essential for gene expression programs that coordinate cell function with metabolic status. However, how these remodelers are integrated in metabolic stability pathways is not well known. Here, we report an expansive genetic screen with chromatin remodelers and metabolic regulators in Saccharomyces cerevisiae. We found that, unlike the SWR1 remodeler, the INO80 chromatin remodeling complex is composed of multiple distinct Functional Subunit modules. We identified a strikingly divergent genetic signature for the Ies6 Subunit module that links the INO80 complex to metabolic homeostasis. In particular, mitochondrial maintenance is disrupted in ies6 mutants. INO80 is also needed to communicate TORC1-mediated signaling to chromatin, as ino80 mutants exhibit defective transcriptional profiles and altered histone acetylation of TORC1-responsive genes. Furthermore, comparative analysis reveals Subunits of INO80 and mTORC1 have high co-occurrence of alterations in human cancers. Collectively, these results demonstrate that the INO80 complex is a central component of metabolic homeostasis that influences histone acetylation and may contribute to disease when disrupted.
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the ino80 chromatin remodeler sustains metabolic stability by promoting tor signaling and regulating histone acetylation
bioRxiv, 2017Co-Authors: Sean L Beckwith, Erin K Schwartz, Pablo E Garcianieto, Devin A King, Graeme J Gowans, Ka Man Wong, Wei Yao, Tessa L Eckley, Alexander P Paraschuk, Egan L PeltanAbstract:Chromatin remodeling complexes are essential for gene expression programs that coordinate cell function with metabolic status. However, how these remodelers are integrated in metabolic stability pathways is not well known. Here, we report an expansive genetic screen with chromatin remodelers and metabolic regulators in Saccharomyces cerevisiae. We found that, unlike the SWR1 remodeler, the INO80 chromatin remodeling complex is composed of multiple distinct Functional Subunit modules. We identified a strikingly divergent genetic signature for the Ies6 Subunit module that links the INO80 complex to metabolic homeostasis, including mitochondrial maintenance. INO80 is also needed to communicate TORC1-mediated signaling to chromatin and maintains histone acetylation at TORC1-responsive genes. Furthermore, computational analysis reveals Subunits of INO80 and mTORC1 have high co-occurrence of alterations in human cancers. Collectively, these results demonstrate that the INO80 complex is a central component of metabolic homeostasis that influences histone acetylation and may contribute to disease when disrupted.
