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The Aryl Hydrocarbon Receptor Nuclear Translocator Arnt Transcriptional Co Regulator Complex
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Book Synopsis The Aryl Hydrocarbon Receptor Nuclear Translocator (ARNT) Transcriptional Co-regulator Complex by : Mark Paul Labrecque
Download or read book The Aryl Hydrocarbon Receptor Nuclear Translocator (ARNT) Transcriptional Co-regulator Complex written by Mark Paul Labrecque and published by . This book was released on 2016 with total page 217 pages. Available in PDF, EPUB and Kindle. Book excerpt:
Book Synopsis Regulation of Eukaryotic Transcription by BHLH/PAS Transcription Factors AhR and Arnt by : Nan Hao
Download or read book Regulation of Eukaryotic Transcription by BHLH/PAS Transcription Factors AhR and Arnt written by Nan Hao and published by . This book was released on 2012 with total page 78 pages. Available in PDF, EPUB and Kindle. Book excerpt: The Aryl hydrocarbon Receptor (AhR) is a Class I basic Helix-Loop-Helix/Per-Arnt-Sim (bHLH/PAS) transcription factor essential for adaptive response to xenobiotics. As for all bHLH/PAS proteins, it has a uniform molecular design that is composed of three functional domains, including a highly conserved N-terminal bHLH domain, a pair of degenerate PAS repeats (designated PAS.A and PAS.B), and a poorly conserved C-terminal transactivation domain. However, in contrast to the other proteins in the family, AhR is the only member known to bind xenobiotic ligand found in nature. The ligand binding domain (LBD) of AhR resides in its PAS.B region. Structure activity relationship analysis suggested that the ligand binding pocket of AhR is promiscuous, which can accommodate a large number of planar and hydrophobic compounds. Polycyclic Aromatic Hydrocarbons (PAHs) and Halogenated Aromatic Hydrocarbons (HAHs) are by far the most common classes of AhR ligands. In addition, pharmaceutical compounds such as the hepatoprotective agent YH439 that fall outside the aromatic classification, have also been shown to activate AhR, presumably by functioning as AhR agonists. To better characterize the LBD of mouse AhR (mAhR), rational site-directed mutagenesis was performed based on the LBD sequences of zebrafish (Danio rerio). Unexpectedly, the mAhR H285Y mutant as well as previously identified A375I mutant were found to discriminate between ligands, suggesting that in contrast to the PAH/HAH ligands, the atypical ligand YH439 has a novel mode of interaction that does not require full access of the ligand binding cavity. All bHLH/PAS proteins function as obligate dimers. In order to form an active, DNA binding complex, the AhR have to dimerize with Class II bHLH/PAS protein Aryl hydrocarbon receptor nuclear translocator (Arnt). This is mediated primarily via the N terminal bHLH and PAS.A domains. Furthermore, the data presented in this thesis suggest that both the [alpha]-helical connector and [beta]-strand structure of the PAS.A domains are required for AhR/Arnt heterodimerization, which is distinct from the [beta]-scaffold surfaces proposed for dimerization between the PAS.B domains of HIF-2[alpha] (Hypoxia Inducible Factor-2[alpha]) and Arnt. Intriguingly, interaction between Arnt and other Class I bHLH/PAS proteins were found to occur via the same dimerization interface, suggesting that the dimerization selectivity of common partner factor Arnt resides on a small number of key amino acids within a single dimerization interface of Arnt. In addition to the canonical AhR activation by xenobiotics, switching cells from adherent to suspension culture also activates the AhR, representing a non-xenobiotic, physiological activation of AhR signaling. This is further supported by the observation that AhR is recruited to the xenobiotic response element (XRE) of prototypical AhR target genes Cyp1a1, Cyp1b1 and Tiparp following both xenobiotic and suspension culture induced AhR activation. However, genome wide microarray analysis revealed significant differences between the two activation mechanisms in modulating target gene expression, implying the existence of a fine-tuning control to define the target gene specificity of AhR. Taken together, the work presented in this thesis explores the various mechanisms underlying AhR regulation with a special emphasis on specificity, which not only advances our current understanding on the non-canonical pathways of AhR activation, but also lends novel insights into how eukaryotic genes are regulated at the transcriptional level.
Book Synopsis Coactivator Dynamics in Aryl Hydrocarbon Receptor Complex Mediated Transcription by : Song Wang
Download or read book Coactivator Dynamics in Aryl Hydrocarbon Receptor Complex Mediated Transcription written by Song Wang and published by . This book was released on 2003 with total page 180 pages. Available in PDF, EPUB and Kindle. Book excerpt:
Book Synopsis Biomarkers in Breast Cancer by : Giampietro Gasparini
Download or read book Biomarkers in Breast Cancer written by Giampietro Gasparini and published by Springer Science & Business Media. This book was released on 2008-01-17 with total page 335 pages. Available in PDF, EPUB and Kindle. Book excerpt: Expert laboratory and clinical researchers from around the world review how to design and evaluate studies of tumor markers and examine their use in breast cancer patients. The authors cover both the major advances in sophisticated molecular methods and the state-of-the-art in conventional prognostic and predictive indicators. Among the topics discussed are the relevance of rigorous study design and guidelines for the validation studies of new biomarkers, gene expression profiling by tissue microarrays, adjuvant systemic therapy, and the use of estrogen, progesterone, and epidermal growth factor receptors as both prognostic and predictive indicators. Highlights include the evaluation of HER2 and EGFR family members, of p53, and of UPA/PAI-1; the detection of rare cells in blood and marrow; and the detection and analysis of soluble, circulating markers.
Book Synopsis Cytochromes P450 by : Costas Ioannides
Download or read book Cytochromes P450 written by Costas Ioannides and published by CRC Press. This book was released on 1996-09-06 with total page 426 pages. Available in PDF, EPUB and Kindle. Book excerpt: Cytochromes P450: Metabolic and Toxicological Aspects examines cytochrome P450 proteins and their role in toxicity/carcinogenicity and the metabolism of foreign chemicals. Studying the function of these proteins enables us to: Predict the pathways and outcome of chemical metabolism to rationalize species, sex, and age differences in toxicity Anticipate drug interactions Modify doses to fit the needs of patients Contributions from internationally acknowledged experts are organized into three sections. The first section provides an overview, the next profiles each of the cytochrome P450 families and subfamilies involved in chemical metabolism, and the last section discusses new issues and developments of current interest. This detailed and thorough examination of cytochrome P450 will be a useful source for research scientists, especially those working in the pharmaceutical industry, dealing with the safety evaluation of chemicals and the study of their metabolism, pharmacokinetics, and toxicological properties.
Book Synopsis Current Trends in Cancer Management by : Liliana Streba
Download or read book Current Trends in Cancer Management written by Liliana Streba and published by BoD – Books on Demand. This book was released on 2019-09-25 with total page 158 pages. Available in PDF, EPUB and Kindle. Book excerpt: The field of cancer diagnosis, prognosis, and treatment is constantly advancing. From novel biomarkers to cutting-edge imaging solutions, changing chemotherapy protocols and novel immune-targeting agents, medical teams develop and test new ways to manage this ever-growing threat to the modern age. Imaging has been a reliable method for initial diagnosis and later surveillance of premalignant and cancerous lesions of the digestive tract. This book project aims to characterize the main diagnostic procedures and novel medical and surgical treatments, as well as provide an updated view on current guidelines, premalignant lesions management, and minimally invasive curative techniques.
Book Synopsis The Guide to Investigation of Mouse Pregnancy by : B. Anne Croy
Download or read book The Guide to Investigation of Mouse Pregnancy written by B. Anne Croy and published by Academic Press. This book was released on 2013-12-09 with total page 829 pages. Available in PDF, EPUB and Kindle. Book excerpt: The Guide to Investigation of Mouse Pregnancy is the first publication to cover the mouse placenta or the angiogenic tree the mother develops to support the placenta. This much-needed resource covers monitoring of the cardiovascular system, gestational programming of chronic adult disease, epigenetic regulation, gene imprinting, and stem cells. Offering detailed and integrated information on how drugs, biologics, stress, and manipulations impact pregnancy in the mouse model, this reference highlights techniques used to analyze mouse pregnancy. Joining the ranks of much referenced mouse resources, The Guide to Investigation of Mouse Pregnancy is the only manual providing needed content on pregnancy in animal models for translational medicine and research. - Provides instruction on how to collect pre-clinical data on pregnancy in mouse models for eventual use in human applications - Describes the angiogenic tree the mother's uterus develops to support pregnancy and the monitoring of pregnancy-induced cardiovascular changes - Educates readers on placental cell lineages, decidual development including immune cells, epigenetic regulation, gene imprinting, stem cells, birth and lactation - Discusses how stress, environmental toxicants and other manipulations impact upon placental function and pregnancy success
Book Synopsis Dancing Protein Clouds: Intrinsically Disordered Proteins in the Norm and Pathology by : Vladimir Uversky
Download or read book Dancing Protein Clouds: Intrinsically Disordered Proteins in the Norm and Pathology written by Vladimir Uversky and published by Academic Press. This book was released on 2019-09-15 with total page 426 pages. Available in PDF, EPUB and Kindle. Book excerpt: "Dancing protein clouds: Intrinsically disordered proteins in the norm and pathology" represents a set of selected studies on a variety of research topics related to intrinsically disordered proteins. Topics in this update include structural and functional characterization of several important intrinsically disordered proteins, such as 14-3-3 proteins and their partners, as well as proteins from muscle sarcomere; representation of intrinsic disorder-related concept of protein structure-function continuum; discussion of the role of intrinsic disorder in phenotypic switching; consideration of the role of intrinsically disordered proteins in the pathogenesis of neurodegenerative diseases and cancer; discussion of the roles of intrinsic disorder in functional amyloids; demonstration of the usefulness of the analysis of translational diffusion of unfolded and intrinsically disordered proteins; consideration of various computational tools for evaluation of functions of intrinsically disordered regions; and discussion of the role of shear stress in the amyloid formation of intrinsically disordered regions in the brain. Provides some recent studies on the intrinsically disordered proteins and their functions, as well as on the involvement of intrinsically disordered proteins in pthogenesis of various diseases Contains numerous illustrative materials (color figures, diagrams, and tables) to help the readers to delve in the information provided Includes contributions from recognized experts in the field
Book Synopsis Encyclopedia of Signaling Molecules by : Sangdun Choi
Download or read book Encyclopedia of Signaling Molecules written by Sangdun Choi and published by Springer. This book was released on 2017-12-15 with total page 6330 pages. Available in PDF, EPUB and Kindle. Book excerpt: The second edition of this encyclopedia presents over 400 biologically important signaling molecules and the content is built on the core concepts of their functions along with early findings written by some of the world’s foremost experts. The molecules are described by recognized leaders in each molecule. The interactions of these single molecules in signal transduction networks will also be explored. This encyclopedia marks a new era in overview of current cellular signaling molecules for the specialist and the interested non-specialist alike. Currently, there are more than 30,000 genes in human genome. However, not all the proteins encoded by these genes work equally in order to maintain homeostasis. Understanding the important signaling molecules as completely as possible will significantly improve our research-based teaching and scientific capabilities.
Book Synopsis Transformation and Translocation of the Human Aromatic Hydrocarbon Receptor, a Comparison of 3-methylcholanthrene and 2,3,7,8-tetrachlorodibenzo-p-dioxin by : Mary A. Holowenko
Download or read book Transformation and Translocation of the Human Aromatic Hydrocarbon Receptor, a Comparison of 3-methylcholanthrene and 2,3,7,8-tetrachlorodibenzo-p-dioxin written by Mary A. Holowenko and published by . This book was released on 1997 with total page 0 pages. Available in PDF, EPUB and Kindle. Book excerpt: The aromatic hydrocarbon receptor (AHR), upon binding ligand, dimerizes with the AH receptor nuclear translocator protein (ARNT) and induces transcriptional activation of many genes, including CYP1A1, by binding to specific dioxin responsive elements (DREs) upstream of the genes. Two classes of ligands, halogenated aromatic hydrocarbons (HAHs) and polycyclic aromatic hydrocarbons (PAHs), while displaying similar binding affinities, show large differences in potency for aryl hydrocarbon hydroxylase (AHH) induction, a selective marker for CYP1A1 activity. The reason for this difference is not fully known. 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) and 3-methylcholanthrene (MC) were compared for their ability to cause transformation and translocation of AHR, key steps in the mechanism of enzyme induction. Evidence is presented for a difference in translocation in LS180 cells. MC-treated cells show more rapid disappearance of nuclear AHR coupled with reappearance of new, functional cytosolic AHR. TCDD-treated cells also show a disappearance of nuclear AHR; however, no new cytosolic AHR protein is synthesized. Using an in vitro system, I found that cytosolic AHR transformed by MC showed a temperature-dependent loss of inducible signal when analyzed by gel retardation assay (GRA). This was not the case with TCDD. Western blot analyses of MC- and TCDD-treated cytosols, however, show no difference in total AHR and ARNT protein levels and indicate that both cytosols contain the AHR-ARNT complex, a form capable of interacting with DNA. These results show that the ability of the AHR complex to interact with DNA depends on ligand. This suggests that AHR-mediated gene expression is not as long-lived with MC as it is with TCDD as the ligand. Hence, the affinity of a ligand for its specific receptor does not necessarily determine its biological potency.
Book Synopsis Translational Immunotherapy of Brain Tumors by : John H. Sampson
Download or read book Translational Immunotherapy of Brain Tumors written by John H. Sampson and published by Academic Press. This book was released on 2017-02-06 with total page 406 pages. Available in PDF, EPUB and Kindle. Book excerpt: Translational Immunotherapy of Brain Tumors gives researchers and practitioners an up-to-date and comprehensive overview of the field. Chapters include adoptive immunotherapy, immunosuppression, CAR therapy of brain tumors, and dendritic cell therapy for brain tumors. Very few agents have been shown to be efficacious in the treatment of malignant gliomas. Recently, there have been a number of studies demonstrating the potential success of immunotherapy for brain tumors. Immunotherapeutics are becoming the most frequent drugs to be used in cancer therapy. These new breakthroughs, now approved by the FDA, are a part of multiple phase III international trials and ongoing research in malignant glioma, meaning that the information in this cutting-edge book will be of great importance to practitioners and researchers alike. Comprehensive overview, providing an update on immunology, translational immunotherapy, and clinical trials relating to malignant gliomas Edited by a prominent neurosurgeon with contributions by leading researchers in the field Ideal resource for researchers and practitioners interested in learning about mechanisms that use the immune system to treat brain tumors
Book Synopsis Analysis of Aryl Hydrocarbon Receptor (AHR) and Aryl Hydrocarbon Receptor Nuclear Translocator (ARNT) in Signal Transduction Processes by : Nikos A. Davarinos
Download or read book Analysis of Aryl Hydrocarbon Receptor (AHR) and Aryl Hydrocarbon Receptor Nuclear Translocator (ARNT) in Signal Transduction Processes written by Nikos A. Davarinos and published by . This book was released on 1999 with total page 248 pages. Available in PDF, EPUB and Kindle. Book excerpt:
Book Synopsis Are All Aryl Hydrocarbon Receptor Agonists Created Equal? by : Danica Elizabeth DeGroot
Download or read book Are All Aryl Hydrocarbon Receptor Agonists Created Equal? written by Danica Elizabeth DeGroot and published by . This book was released on 2012 with total page pages. Available in PDF, EPUB and Kindle. Book excerpt: The aryl hydrocarbon receptor (AhR) is a ligand-activated transcription factor belonging to the basic-helix-loop-helix-Per/ARNT/Sim (bHLH/PAS) family of regulatory proteins. While the best characterized and highest affinity AhR ligands are the halogenated aromatic hydrocarbons (HAHs), including 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD, dioxin), and the polycyclic aromatic hydrocarbons (PAHs), the AhR can also bind and be activated by structurally diverse synthetic and naturally occurring compounds. The AhR resides in the cytosol until ligand binding promotes nuclear translocation and heterodimerization with the AhR nuclear translocator protein (ARNT). Binding of the ligand:AhR:ARNT complex to its specific DNA recognition site, the dioxin responsive element (DRE), stimulates transcription of downstream genes such as cytochrome P4501A1. Although the sequence of the DRE is well defined, several reports have suggested that the nucleotide specificity of AhR DNA binding may be ligand-dependent. In this report, we have identified novel AhR agonists and characterized the effects of several nonclassical AhR activators on AhR:ARNT DNA binding. Eight naturally-occurring, marine-derived brominated indoles were characterized as AhR agonists using AhR-responsive recombinant cell bioassays systems generated in mouse, rat, and guinea pig cell lines. Competitive binding analysis using the murine AhR confirmed several of these compounds as potent AhR ligands. Next, detailed DNA binding analysis and functional assays were utilized to examine two ligand-specific DRE-like response elements reported to confer AhR:ARNT-dependent responsiveness to PAHs and other compounds, but not to TCDD. We failed to validate either sequence as a binding site for the AhR:ARNT complex regardless of the bound ligand, and also demonstrated that neither sequence stimulated AhR-dependent reporter gene expression. These results led to a more systematic evaluation of AhR:ARNT DNA binding. A relatively unbiased DNA selection and PCR-based amplification assay isolated DNA sequences bound to the AhR activated by structurally diverse AhR ligands. All ligand-activated AhR:ARNT complexes specifically bound to DNA containing the defined DRE recognition sequence. Our results are consistent with the established role of the canonical DRE sequence as the AhR DNA binding site for ligand-activated AhR:ARNT complexes and that binding of structurally diverse agonists to the AhR does not alter its nucleotide specificity of DNA binding.
Book Synopsis Studies Into the Aryl Hydrocarbon Receptor Signaling Pathway by : Shawn David Seidel
Download or read book Studies Into the Aryl Hydrocarbon Receptor Signaling Pathway written by Shawn David Seidel and published by . This book was released on 1999 with total page 364 pages. Available in PDF, EPUB and Kindle. Book excerpt:
Book Synopsis Analysis of Aryl Hydrocarbon Receptor Nuclear Translocator (ARNT) Protein Expression and Concentration in Aquatic and Mammalian Models by : Jennifer L. Holmes
Download or read book Analysis of Aryl Hydrocarbon Receptor Nuclear Translocator (ARNT) Protein Expression and Concentration in Aquatic and Mammalian Models written by Jennifer L. Holmes and published by . This book was released on 1997 with total page 218 pages. Available in PDF, EPUB and Kindle. Book excerpt:
Book Synopsis Hormonally Active Agents in the Environment by : National Research Council
Download or read book Hormonally Active Agents in the Environment written by National Research Council and published by National Academies Press. This book was released on 2000-02-03 with total page 453 pages. Available in PDF, EPUB and Kindle. Book excerpt: Some investigators have hypothesized that estrogens and other hormonally active agents found in the environment might be involved in breast cancer increases and sperm count declines in humans as well as deformities and reproductive problems seen in wildlife. This book looks in detail at the science behind the ominous prospect of "estrogen mimics" threatening health and well-being, from the level of ecosystems and populations to individual people and animals. The committee identifies research needs and offers specific recommendations to decision-makers. This authoritative volume: Critically evaluates the literature on hormonally active agents in the environment and identifies known and suspected toxicologic mechanisms and effects of fish, wildlife, and humans. Examines whether and how exposure to hormonally active agents occursâ€"in diet, in pharmaceuticals, from industrial releases into the environmentâ€"and why the debate centers on estrogens. Identifies significant uncertainties, limitations of knowledge, and weaknesses in the scientific literature. The book presents a wealth of information and investigates a wide range of examples across the spectrum of life that might be related to these agents.
Book Synopsis Microbiome and Metabolome in Diagnosis, Therapy, and other Strategic Applications by : Joel Faintuch
Download or read book Microbiome and Metabolome in Diagnosis, Therapy, and other Strategic Applications written by Joel Faintuch and published by Academic Press. This book was released on 2019-01-03 with total page 506 pages. Available in PDF, EPUB and Kindle. Book excerpt: Microbiome and Metabolome in Diagnosis, Therapy, and Other Strategic Applications is the first book to simultaneously cover the microbiome and the metabolome in relevant clinical conditions. In a pioneering fashion, it addresses not only the classic intestinal environment, but also the oral, gastric, lung, skin and vaginal microbiome that is in line with the latest investigations. Nonbacterial microbiomes, such as fungi and viruses are not overlooked, and the plasma microbiome is also discussed. As plasma, brain, placenta, tumor cells, and other sterile fluids and tissues, are increasingly recognized to potentially host a microbiome, albeit a limited one, this is a timely resource. The book's editors were fortunate to have the input of renowned collaborators from nearly all continents. This is truly an international effort that brings the latest in the field to students and professionals alike. - Provides comprehensive coverage on diagnosis, therapy, pharmacotherapy and disease prevention in context of the microbiome and metabolome - Focuses on the proposed physiological or pathological conditions - Presents an up-to-date, useful reference
