scholarly journals Structure of the p53 Transactivation Domain in Complex with the Nuclear Receptor Coactivator Binding Domain of CREB Binding Protein

Biochemistry ◽  
2010 ◽  
Vol 49 (46) ◽  
pp. 9964-9971 ◽  
Author(s):  
Chul Won Lee ◽  
Maria A. Martinez-Yamout ◽  
H. Jane Dyson ◽  
Peter E. Wright
Keyword(s):  
Nuclear Receptor ◽  
Binding Protein ◽  
Binding Domain ◽  
Transactivation Domain ◽  
Creb Binding Protein ◽  
Nuclear Receptor Coactivator

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 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 Nuclear Factor of Activated T Cells (NFAT)-dependent Transactivation Regulated by the Coactivators p300/CREB-binding Protein (CBP)

1998 ◽  
Vol 187 (12) ◽  
pp. 2031-2036 ◽  
Author(s):  
Carmen García-Rodríguez ◽  
Anjana Rao
Keyword(s):  
T Cells ◽  
Binding Protein ◽  
Critical Role ◽  
Regulation Of Transcription ◽  
Dependent Manner ◽  
Nuclear Factor ◽  
Transactivation Domain ◽  
Creb Binding Protein ◽  
Activated T Cells ◽  
Viral Oncoprotein

p300 and cAMP response element–binding protein (CREB)–binding protein (CBP) are members of a family of coactivators involved in the regulation of transcription and chromatin. We show that transcription factors of the nuclear factor of activated T cells (NFAT) family bind p300/CBP and recruit histone acetyltransferase activity from T cell nuclear extracts. The NH2-terminal transactivation domain of NFAT1 and the phospho-CREB- and E1A-binding sites of p300/CBP are involved in the interaction. The viral oncoprotein E1A inhibits NFAT-dependent transactivation in a p300-dependent manner. Recruitment of the coactivators p300/CBP by the transactivation domains of NFAT proteins is likely to play a critical role in NFAT-dependent gene expression during the immune response.

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 Site-Specific Acetylation by p300 or CREB Binding Protein Regulates Erythroid Krüppel-Like Factor Transcriptional Activity via Its Interaction with the SWI-SNF Complex

2001 ◽  
Vol 21 (7) ◽  
pp. 2413-2422 ◽  
Author(s):  
Wenjun Zhang ◽  
Shilpa Kadam ◽  
Beverly M. Emerson ◽  
James J. Bieker
Keyword(s):  
Chromatin Structure ◽  
Binding Protein ◽  
Globin Gene ◽  
Critical Role ◽  
Erythroid Cell ◽  
Transactivation Domain ◽  
Creb Binding Protein ◽  
Site Specific ◽  
Acetylation Status

ABSTRACT Recruitment of modifiers and remodelers to specific DNA sites within chromatin plays a critical role in controlling gene expression. The study of globin gene regulation provides a convergence point within which to address these issues in the context of tissue-specific and developmentally regulated expression. In this regard, erythroid Krüppel-like factor (EKLF) is critical. EKLF is a red cell-specific activator whose presence is crucial for establishment of the correct chromatin structure and high-level transcriptional induction of adult β-globin. We now find, by metabolic labeling-immunoprecipitation experiments, that EKLF is acetylated in the erythroid cell. EKLF residues acetylated by CREB binding protein (CBP) in vitro map to Lys-288 in its transactivation domain and Lys-302 in its zinc finger domain. Although site-specific DNA binding by EKLF is unaffected by the acetylation status of either of these lysines, directed mutagenesis of Lys-288 (but not Lys-302) decreases the ability of EKLF to transactivate the β-globin promoter in vivo and renders it unable to be superactivated by coexpressed p300 or CBP. In addition, the acetyltransferase function of CBP or p300 is required for superactivation of wild-type EKLF. Finally, acetylated EKLF has a higher affinity for the SWI-SNF chromatin remodeling complex and is a more potent transcriptional activator of chromatin-assembled templates in vitro. These results demonstrate that the acetylation status of EKLF is critical for its optimal activity and suggest a mechanism by which EKLF acts as an integrator of remodeling and transcriptional components to alter chromatin structure and induce adult β-globin expression within the β-like globin cluster.

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