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A High-Throughput Screening Method to Identify Small Molecule Inhibitors of Thyroid Hormone Receptor Coactivator Binding

To provide alternative methods for regulation of gene transcription initiated by the binding of thyroid hormone (T3) to the thyroid receptor (TR), we have developed a high-throughput method for discovering inhibitors of the interaction of TR with its transcriptional coactivators. The screening method is based on fluorescence polarization (FP), one of the most sensitive and robust high-throughput methods for the study of protein-protein interactions. A fluorescently labeled coactivator is excited by polarized light. The emitted polarized light is a function of the molecular properties of the labeled coactivator, especially Brownian molecular rotation, which is very sensitive to changes in the molecular mass of the labeled complex. Dissociation of hormone receptor from fluorescently labeled coactivator peptide in the presence of small molecules can be detected by this competition method, and the assay can be performed in a high-throughput screening format. Hit compounds identified by this method are evaluated by several secondary assay methods, including a dose-response analysis, a semiquantitative glutathione-S-transferase assay, and a hormone displacement assay. Subsequent in vitro transcription assays can detect inhibition of thyroid signaling at low micromolar concentrations of small molecules in the presence of T3.

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Resource Type: Diagram, Image, Journal, Journal article/Issue, Laboratory manual
Discipline: Cell biology, Developmental Biology, Metabolism, Microbiology, Molecular Biology
Pedagogical Use: Learn
Audience Level: Undergraduate upper division 15-16, Graduate, Professional (degree program)

Author and Copyright


Authors and Editors: Leggy A. Arnold of University of California, San Francisco, Eva Estebanez-Perpina of University of California, San Francisco, Marie Togashi of University of California, San Francisco, Anang Shelat of University of California, San Francisco, Cory A. Ocasio of University of California, San Francisco, Andrea C. McReynolds of University of California, San Francisco, Phuong Nguyen of University of California, San Francisco, John D. Baxter, Robert J. Fletterick, Paul Webb, R. Kiplin Guy
Publisher: American Association for the Advancement of Science
Date Published: 2006-06-27
Date Added to BEN: 2013-05-11
Format: application/pdf, image/gif, image/jpeg, text/html
Copyright and other restrictions: Yes
Cost: Yes
Cost Description: Copyright © 2006 by the American Association for the Advancement of Science and the Board of Trustees of the Leland Stanford Junior University

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Collection:
STKE/Science Signaling



A Hitchhiker's Guide to the Proteasome

Regulated degradation of proteins is essential for viability and is involved in the control of many signal transduction pathways. von Arnim discusses a new model for how substrates destined for degradation by the 26S proteasome may be presented to the proteasome through a physical interaction between the proteasome and a complex consisting of the substrate and a ubiquitin-ligase. The new model suggests that the SCF (Skp1/cullin/F-box) protein complex may physically associate with the proteasome and that this interaction may be regulated by posttranslational modifications, such as phosphorylation or the covalent attachment of the Nedd8 protein, called neddylation. Additionally, other proteins may compete with the SCF complexes for binding to the proteasome and thus present another layer of regulation for controlling substrate targeting for ubiquitin-mediated degradation.

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Resource Type: Diagram, Illustration, Journal article/Issue, Review
Discipline: Biochemistry, Botany & Plant Science, Cell biology, Molecular Biology
Pedagogical Use: Learn, Research, Teach
Audience Level: Undergraduate upper division 15-16, Graduate, Professional (degree program)

Author and Copyright


Authors and Editors: Albrecht G. von Arnim of Department of Botany, University of Tennessee
Publisher: American Association for the Advancement of Science
Date Published: 2001-08-28
Date Added to BEN: 2004-09-02
Format: application/pdf, image/gif, image/jpeg, text/html
Copyright and other restrictions: Yes
Cost: Yes
Cost Description: Copyright American Association for the Advancement of Science

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Collection:
STKE/Science Signaling



A Hover-fly Transports Pollinia Among Flowers of Epipactis helleborine (L.) Crantz

A hover-fly transports pollinia among flowers of Epipactis helleborine (L.) Crantz in England. Dominantly wasp-mediated cross-pollination has generated genetic structures consistent with random mating in both European and introduced North American populations.

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Resource Type: Image
Discipline: Botany & Plant Science
Audience Level: High school lower division 9-10, High school upper division 11-12, Undergraduate lower division 13-14, Undergraduate upper division 15-16, Graduate

Author and Copyright


Authors and Editors: Karl Niklas of Boptany Department, Cornell University, Richard M. Bateman of Natural History Museum
Date Published: 2004-03-09
Date Added to BEN: 2004-03-08
Format: image/jpeg
Copyright and other restrictions: Yes
Cost: No
Cost Description: Use of the site is limited to free use in a nonprofit educational or private non-commercial context. Images remain the property of the copyright holder, who retains all rights implicit in copyright laws and other rights to the images not enumerated here for worldwide use. Images may be stored for personal or classroom use, provided that the image displays the unaltered text watermark. All rights to reproduce these images are retained by the Botanical Society of America and the copyright owner. By accessing these images, you are consenting to our licensing agreement. By mentioning these rights, we are just underscoring that those who donated these images should get credit for them and receive any nominal fees should a publisher decide to use these images in a book or CD.

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Collection:
Botanical Society of America



A Hypothesis About the Role of Adult Neurogenesis in Hippocampal Function - Figure 1

This figure shows neurogenesis in the adult dentate gyrus.

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Resource Type: Digital Presentation (Powerpoint), Illustration, Image, Journal Article/Issue
Discipline: Education, Neurobiology/Neuroscience, Physiology
Pedagogical Use: learn
Audience Level: Undergraduate lower division (Grades 13-14), Undergraduate upper division (Grades 15-16), Graduate, Professional (degree program), General Public, Informal Education, Continuing Education

Author and Copyright


Authors and Editors: PhD Alejandro F. Schinder of Leloir Institute Foundation, Fred H. Gage of The Salk Institute Laboratory of Genetics
Date Published: 2004-10-01
Date Added to BEN: 2011-11-05
Format: text/html
Copyright and other restrictions: No
Cost: No

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Collection:
American Physiological Society



A Hypothesis About the Role of Adult Neurogenesis in Hippocampal Function - Figure 2

This figure describes neurogenesis and the synaptic plasticity; and memory hypothesis.

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Resource Type: Digital Presentation (Powerpoint), Graph/Chart, Image, Journal Article/Issue
Discipline: Education, Neurobiology/Neuroscience, Physiology
Pedagogical Use: learn
Audience Level: Undergraduate lower division (Grades 13-14), Undergraduate upper division (Grades 15-16), Graduate, Professional (degree program), General Public, Informal Education, Continuing Education

Author and Copyright


Authors and Editors: PhD Alejandro F. Schinder of Leloir Institute Foundation, Fred H. Gage of The Salk Institute Laboratory of Genetics
Date Published: 2004-10-01
Date Added to BEN: 2011-11-05
Format: text/html
Copyright and other restrictions: No
Cost: No

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Collection:
American Physiological Society



A Kelch {beta} Propeller Featuring as a G{beta} Structural Mimic: Reinventing the Wheel?

New genetic and protein interaction data suggest that G protein α subunits may have partners with primary sequences that are quite divergent. How this is achieved may be through the adoption of similar structures, the β propeller, by both proteins containing WD-40 repeats and kelch domains. Gettemans et al. describe results in yeast that suggest that kelch-domain proteins may serve as previously unrecognized β subunits in the heterotrimeric G protein complex.

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Resource Type: Diagram, Illustration, Journal article/Issue, Review
Discipline: Biochemistry, Cell biology, Microbiology, Molecular Biology, Structural biology
Pedagogical Use: Learn, Research, Teach
Audience Level: Undergraduate upper division 15-16, Graduate, Professional (degree program)

Author and Copyright


Authors and Editors: Jan Gettemans of Department of Biochemistry, Rommelaere Institute, Kris Meerschaert of Faculty of Medicine and Health Sciences, Rommelaere Institute, Joel Vandekerckhove of Flanders Interuniversity Institute for Biotechnology (VIB), Rommelaere Institute, Veerle De Corte of Ghent University, Rommelaere Institute
Publisher: American Association for the Advancement of Science
Date Published: 2003-07-15
Date Added to BEN: 2003-12-23
Format: application/pdf, image/gif, image/jpeg, text/html
Copyright and other restrictions: Yes
Cost: Yes
Cost Description: Copyright 2003 American Association for the Advancement of Science

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Collection:
STKE/Science Signaling



A Leaflet of Rhus toxicodendroides, a Fossil Plant from the Los Ahuehuetes Locality, Puebla, Mexico

A leaflet of Rhus toxicodendroides, a fossil plant from the Los Ahuehuetes locality, Puebla, Mexico, a center of diversity for the Anacardiaceae since the Oligocene, suggesting that the area was important for the radiation and diversification for some lineages within the family.

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Classifications


Resource Type: Image
Discipline: Botany & Plant Science
Audience Level: High school lower division 9-10, High school upper division 11-12, Undergraduate lower division 13-14, Undergraduate upper division 15-16, Graduate

Author and Copyright


Authors and Editors: Karl Niklas of Cornell University, Hector Hernández Campos
Date Published: 2004-03-09
Date Added to BEN: 2004-03-08
Format: image/jpeg
Copyright and other restrictions: Yes
Cost: No
Cost Description: Use of the site is limited to free use in a nonprofit educational or private non-commercial context. Images remain the property of the copyright holder, who retains all rights implicit in copyright laws and other rights to the images not enumerated here for worldwide use. Images may be stored for personal or classroom use, provided that the image displays the unaltered text watermark. All rights to reproduce these images are retained by the Botanical Society of America and the copyright owner. By accessing these images, you are consenting to our licensing agreement. By mentioning these rights, we are just underscoring that those who donated these images should get credit for them and receive any nominal fees should a publisher decide to use these images in a book or CD.

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Collection:
Botanical Society of America



A Life Science Semantic Web: Are We There Yet?

More than ever, life science researchers depend on information from multiple sources. The Semantic Web offers a powerful new strategy for consolidating both text and structured data into a comprehensive collections and views. In addition, these aggregates are readable by both humans and machines and could be the basis of information management and knowledge exchange.

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Classifications


Resource Type: Diagram, Illustration, Journal article/Issue, Review
Discipline: Bioinformatics Genomics & Proteomics
Pedagogical Use: Learn, Research, Teach
Audience Level: Undergraduate upper division 15-16, Graduate, Professional (degree program)

Author and Copyright


Authors and Editors: Eric Neumann of Sanofi-Aventis Pharmaceuticals
Publisher: American Association for the Advancement of Science
Date Published: 2005-05-10
Date Added to BEN: 2005-10-25
Format: application/pdf, image/gif, image/jpeg, text/html
Copyright and other restrictions: Yes
Cost: Yes
Cost Description: Copyright © 2005 by the American Association for the Advancement of Science

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Collection:
STKE/Science Signaling



A Ligand-Receptor Mechanism in Plant-Pathogen Recognition

Access to the article is free, however registration and sign-in are required. Two reports in this issue (p. 2060 and p. 2063) illustrate the molecular mechanism underlying the specificity of plant pathogens for certain plant species. In his Perspective, Lamb explains what these results teach us about signal transduction pathways in plants and how they provide a new tool for engineering crop plants.

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Classifications


Resource Type: Journal article/Issue, Review, Diagram
Discipline: Biochemistry, Botany & Plant Science, Evolutionary Biology, Genetics & Heredity, Molecular Biology, Pathology
Pedagogical Use: Learn, Research, Teach
Audience Level: High school upper division 11-12, Undergraduate lower division 13-14, Undergraduate upper division 15-16, Graduate

Author and Copyright


Authors and Editors: Chris Lamb of Plant Biology Laboratory, Salk Institute for Biological Studies
Publisher: AAAS
Date Published: 1996-12-20
Date Added to BEN: 2011-10-29
Format: text/html
Copyright and other restrictions: Yes
Cost: No
Cost Description: Access to the article is free, however registration and sign-in are required. © Copyright AAAS. All rights reserved.

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Collection:
American Association for the Advancement of Science



A Long Search for Glut4 Activation

Insulin stimulates glucose transport in its target cells by translocation of the glucose transporter isoform 4 (Glut4) from an intracellular storage pool to the plasma membrane. A large body of evidence indicates that activity of Glut4 at the plasma membrane may vary. Recent findings suggest that p38 MAPK may be involved in regulation of the intrinsic activity of the transporter.

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Classifications


Resource Type: Diagram, Illustration, Journal article/Issue, Review
Discipline: Biochemistry, Cell biology, Molecular Biology
Pedagogical Use: Learn, Research, Teach
Audience Level: Undergraduate upper division 15-16, Graduate, Professional (degree program)

Author and Copyright


Authors and Editors: Konstantin V. Kandror of Boston University School of Medicine
Publisher: American Association for the Advancement of Science
Date Published: 2003-02-11
Date Added to BEN: 2003-12-23
Format: application/pdf, image/gif, image/jpeg, text/html
Copyright and other restrictions: Yes
Cost: Yes
Cost Description: Copyright 2003 American Association for the Advancement of Science

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Collection:
STKE/Science Signaling



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