scholarly journals Biochemical and NMR Mapping of the Interface between CREB-binding Protein and Ligand Binding Domains of Nuclear Receptor

2004 ◽  
Vol 280 (7) ◽  
pp. 5682-5692 ◽  
Author(s):  
Fabrice A. C. Klein ◽  
R. Andrew Atkinson ◽  
Noelle Potier ◽  
Dino Moras ◽  
Jean Cavarelli
Keyword(s):  
Ligand Binding ◽  
Nuclear Receptor ◽  
Binding Protein ◽  
Creb Binding Protein ◽  
Binding Domains

scholarly journals Mapping the Membrane Topology and Extracellular Ligand Binding Domains of the Retinol Binding Protein Receptor†

Biochemistry ◽  
2008 ◽  
Vol 47 (19) ◽  
pp. 5387-5395 ◽  
Author(s):  
Riki Kawaguchi ◽  
Jiamei Yu ◽  
Patrick Wiita ◽  
Mariam Ter-Stepanian ◽  
Hui Sun
Keyword(s):  
Ligand Binding ◽  
Binding Protein ◽  
Membrane Topology ◽  
Retinol Binding Protein ◽  
Binding Domains ◽  
Protein Receptor

scholarly journals Multiple Signal Input and Output Domains of the 160-Kilodalton Nuclear Receptor Coactivator Proteins

1999 ◽  
Vol 19 (9) ◽  
pp. 6164-6173 ◽  
Author(s):  
Han Ma ◽  
Heng Hong ◽  
Shih-Ming Huang ◽  
Ryan A. Irvine ◽  
Paul Webb ◽  
...  
Keyword(s):  
Nuclear Receptor ◽  
Transcriptional Activation ◽  
Thyroid Hormone Receptor ◽  
Activation Function ◽  
Creb Binding Protein ◽  
Activation Domain ◽  
Nuclear Receptor Coactivator ◽  
Interacting Protein ◽  
Binding Domains ◽  
Signal Input

ABSTRACT Members of the 160-kDa nuclear receptor coactivator family (p160 coactivators) bind to the conserved AF-2 activation function found in the hormone binding domains of nuclear receptors (NR) and are potent transcriptional coactivators for NRs. Here we report that the C-terminal region of p160 coactivators glucocorticoid receptor interacting protein 1 (GRIP1), steroid receptor coactivator 1 (SRC-1a), and SRC-1e binds the N-terminal AF-1 activation function of the androgen receptor (AR), and p160 coactivators can thereby enhance transcriptional activation by AR. While they all interact efficiently with AR AF-1, these same coactivators have vastly different binding strengths with and coactivator effects on AR AF-2. p160 activation domain AD1, which binds secondary coactivators CREB binding protein (CBP) and p300, was previously implicated as the principal domain for transmitting the activating signal to the transcription machinery. We identified a new highly conserved motif in the AD1 region which is important for CBP/p300 binding. Deletion of AD1 only partially reduced p160 coactivator function, due to signaling through AD2, another activation domain located at the C-terminal end of p160 coactivators. C-terminal coactivator fragments lacking AD1 but containing AD2 and the AR AF-1 binding site served as efficient coactivators for full-length AR and AR AF-1. The two signal input domains (one that binds NR AF-2 domains and one that binds AF-1 domains of some but not all NRs) and the two signal output domains (AD1 and AD2) of p160 coactivators played different relative roles for two different NRs: AR and thyroid hormone receptor.

scholarly journals A New Family of Nuclear Receptor Coregulators That Integrate Nuclear Receptor Signaling through CREB-Binding Protein

2000 ◽  
Vol 20 (14) ◽  
pp. 5048-5063 ◽  
Author(s):  
Muktar A. Mahajan ◽  
Herbert H. Samuels
Keyword(s):  
Nuclear Receptor ◽  
Hormone Receptors ◽  
Binding Protein ◽  
Nuclear Hormone Receptors ◽  
Dependent Manner ◽  
Creb Binding Protein ◽  
Activation Domain ◽  
High Affinity ◽  
New Family ◽  
Nuclear Receptor Coregulators

ABSTRACT We describe the cloning and characterization of a new family of nuclear receptor coregulators (NRCs) which modulate the function of nuclear hormone receptors in a ligand-dependent manner. NRCs are expressed as alternatively spliced isoforms which may exhibit different intrinsic activities and receptor specificities. The NRCs are organized into several modular structures and contain a single functional LXXLL motif which associates with members of the steroid hormone and thyroid hormone/retinoid receptor subfamilies with high affinity. Human NRC (hNRC) harbors a potent N-terminal activation domain (AD1), which is as active as the herpesvirus VP16 activation domain, and a second activation domain (AD2) which overlaps with the receptor-interacting LXXLL region. The C-terminal region of hNRC appears to function as an inhibitory domain which influences the overall transcriptional activity of the protein. Our results suggest that NRC binds to liganded receptors as a dimer and this association leads to a structural change in NRC resulting in activation. hNRC binds CREB-binding protein (CBP) with high affinity in vivo, suggesting that hNRC may be an important functional component of a CBP complex involved in mediating the transcriptional effects of nuclear hormone receptors.

Temporal/spatial expression of nuclear receptor coactivators in the mouse lung

2000 ◽  
Vol 279 (6) ◽  
pp. L1066-L1074 ◽  
Author(s):  
Angela Naltner ◽  
Susan Wert ◽  
Jeffrey A. Whitsett ◽  
Cong Yan
Keyword(s):  
Retinoic Acid ◽  
Epithelial Cells ◽  
Nuclear Receptor ◽  
Binding Protein ◽  
Mouse Lung ◽  
Alveolar Type ◽  
Type I ◽  
Type Ii ◽  
Creb Binding Protein ◽  
Nuclear Receptor Coactivators

Our laboratory has previously demonstrated that retinoic acid nuclear receptor, thyroid transcription factor-1 (TTF-1), and nuclear receptor coactivators such as cAMP response element binding protein (CREB) binding protein (CBP)/p300 and steroid receptor coactivator-1 (SRC-1) form an enhanceosome on the 5′-enhancer region of the human surfactant protein B gene. Immunohistochemistry was used to identify cells that coexpressed CBP/p300, SRC-1, retinoid X receptor, and TTF-1 in the developing and mature lung. CBP/p300 and SRC-1 were expressed in the adult mouse lung, CBP and p300 being present in both alveolar type I and type II epithelial cells and SRC-1 and TTF-1 being restricted to type II epithelial cells. CBP/p300, SRC-1, and TTF-1 were readily detected in the nuclei of developing respiratory epithelial tubules in fetal mice from embryonic days 10 to 18.CBP/p300 and SRC-1 were also detected in developing mesenchymal cells. These coactivators were coexpressed with TTF-1 and SP-B in human pulmonary adenocarcinoma cells (H441 cells) in vitro. Interaction assays with a two-hybrid reporter analysis demonstrated direct interactions among TTF-1, SRC-1, and CBP/p300 in H441 cells. These findings support a role for retinoic acid receptor and nuclear receptor coactivators in the regulation of SP-B gene expression in the respiratory epithelium.

scholarly journals Multiple functions and essential roles of nuclear receptor coactivators of bHLH-PAS family

2016 ◽  
Vol 50 (3) ◽  
pp. 165-181 ◽  
Author(s):  
L. Pecenova ◽  
Robert Farkas
Keyword(s):  
Transcription Factors ◽  
Ligand Binding ◽  
Nuclear Receptor ◽  
Covalent Modification ◽  
Cooperative Action ◽  
Animal Development ◽  
Binding Domains ◽  
Nuclear Receptor Coactivators ◽  
Coregulatory Proteins ◽  
Steroid Receptor Coactivators

Abstract Classical non-peptide hormones, such as steroids, retinoids, thyroid hormones, vitamin D3 and their derivatives including prostaglandins, benzoates, oxysterols, and bile acids, are collectively designated as small lipophilic ligands, acting via binding to the nuclear receptors (NRs). The NRs form a large superfamily of transcription factors that participate virtually in every key biological process. They control various aspects of animal development, fertility, gametogenesis, and numerous metabolic pathways, and can be misregulated in many types of cancers. Their enormous functional plasticity, as transcription factors, relates in part to NR-mediated interactions with plethora of coregulatory proteins upon ligand binding to their ligand binding domains (LBD), or following covalent modification. Here, we review some general views of a specific group of NR coregulators, so-called nuclear receptor coactivators (NRCs) or steroid receptor coactivators (SRCs) and highlight some of their unique functions/roles, which are less extensively mentioned and discussed in other reviews. We also try to pinpoint few neglected moments in the cooperative action of SRCs, which may also indicate their variable roles in the hormone-independent signaling pathways.

Nuclear-Receptor Ligands and Ligand-Binding Domains

1999 ◽  
Vol 68 (1) ◽  
pp. 559-581 ◽  
Author(s):  
Ross V. Weatherman ◽  
Robert J. Fletterick ◽  
Thomas S. Scanlan
Keyword(s):  
Ligand Binding ◽  
Nuclear Receptor ◽  
Receptor Ligands ◽  
Binding Domains ◽  
Nuclear Receptor Ligands
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