CBP, a transcriptional coactivator and acetyltransferase

2001 ◽  
Vol 79 (3) ◽  
pp. 253-266 ◽  
Author(s):  
Kirk J McManus ◽  
Michael J Hendzel
Keyword(s):  
Binding Protein ◽  
Creb Binding Protein ◽  
Transcriptional Coactivator ◽  
Molecular Scaffold ◽  
Acetyltransferase Activity ◽  
Large Size ◽  
Multiple Protein ◽  
Element Binding Protein ◽  
Cyclic Amp Response Element ◽  
Chromatin Acetylation

The CREB binding protein (CBP) was first identified as a protein that specifically binds to the active phosphorylated form of the cyclic-AMP response element binding protein (CREB). CBP was initially defined as a transcriptional coactivator that, as a result of its large size and multiple protein binding domain modules, may function as a molecular scaffold. More recently, an acetyltransferase activity, both of histones and nonhistones, has been found to be essential for transactivation. In this review, we will discuss the current understanding of the acetyltransferase specificity and activity of the CBP protein and how it may function to coactivate transcription. We will also examine the regulation of the CBP histone acetyltransferase activity in the cell cycle, by signal-transduction pathways and throughout development.Key words: CBP, acetyltransferase, chromatin, acetylation, p300.

scholarly journals Transcriptional Activation by NF-κB Requires Multiple Coactivators

1999 ◽  
Vol 19 (9) ◽  
pp. 6367-6378 ◽  
Author(s):  
Kelly-Ann Sheppard ◽  
David W. Rose ◽  
Zaffar K. Haque ◽  
Riki Kurokawa ◽  
Eileen McInerney ◽  
...  
Keyword(s):  
Gene Expression ◽  
Transcriptional Activation ◽  
Histone Acetyltransferase ◽  
Binding Protein ◽  
Nuclear Factor Κb ◽  
Nuclear Factor ◽  
Creb Binding Protein ◽  
Element Binding Protein ◽  
Cyclic Amp Response Element ◽  
Coactivator Complex

ABSTRACT Nuclear factor-κB (NF-κB) plays a role in the transcriptional regulation of genes involved in inflammation and cell survival. In this report we demonstrate that NF-κB recruits a coactivator complex that has striking similarities to that recruited by nuclear receptors. Inactivation of either cyclic AMP response element binding protein (CREB)-binding protein (CBP), members of the p160 family of coactivators, or the CBP-associated factor (p/CAF) by nuclear antibody microinjection prevents NF-κB-dependent transactivation. Like nuclear receptor-dependent gene expression, NF-κB-dependent gene expression requires specific LXXLL motifs in one of the p160 family members, and enhancement of NF-κB activity requires the histone acetyltransferase (HAT) activity of p/CAF but not that of CBP. This coactivator complex is differentially recruited by members of the Rel family. The p50 homodimer fails to recruit coactivators, although the p50-p65 heterodimeric form of the transcription factor assembles the integrator complex. These findings provide new mechanistic insights into how this family of dimeric transcription factors has a differential effect on gene expression.

scholarly journals Recognition of the disordered p53 transactivation domain by the transcriptional adapter zinc finger domains of CREB-binding protein

2016 ◽  
Vol 113 (13) ◽  
pp. E1853-E1862 ◽  
Author(s):  
Alexander S. Krois ◽  
Josephine C. Ferreon ◽  
Maria A. Martinez-Yamout ◽  
H. Jane Dyson ◽  
Peter E. Wright
Keyword(s):  
Binding Protein ◽  
Isotopic Labeling ◽  
Structural Basis ◽  
Transactivation Domain ◽  
Creb Binding Protein ◽  
Intrinsically Disordered ◽  
Binary Complexes ◽  
Element Binding Protein ◽  
Cyclic Amp Response Element ◽  
Exchange Broadening

An important component of the activity of p53 as a tumor suppressor is its interaction with the transcriptional coactivators cyclic-AMP response element-binding protein (CREB)-binding protein (CBP) and p300, which activate transcription of p53-regulated stress response genes and stabilize p53 against ubiquitin-mediated degradation. The highest affinity interactions are between the intrinsically disordered N-terminal transactivation domain (TAD) of p53 and the TAZ1 and TAZ2 domains of CBP/p300. The NMR spectra of simple binary complexes of the TAZ1 and TAZ2 domains with the p53TAD suffer from exchange broadening, but innovations in construct design and isotopic labeling have enabled us to obtain high-resolution structures using fusion proteins, uniformly labeled in the case of the TAZ2–p53TAD fusion and segmentally labeled through transintein splicing for the TAZ1–p53TAD fusion. The p53TAD is bipartite, with two interaction motifs, termed AD1 and AD2, which fold to form short amphipathic helices upon binding to TAZ1 and TAZ2 whereas intervening regions of the p53TAD remain flexible. Both the AD1 and AD2 motifs bind to hydrophobic surfaces of the TAZ domains, with AD2 making more extensive hydrophobic contacts consistent with its greater contribution to the binding affinity. Binding of AD1 and AD2 is synergistic, and structural studies performed with isolated motifs can be misleading. The present structures of the full-length p53TAD complexes demonstrate the versatility of the interactions available to an intrinsically disordered domain containing bipartite interaction motifs and provide valuable insights into the structural basis of the affinity changes that occur upon stress-related posttranslational modification.

scholarly journals p300/cAMP-response-element-binding-protein ('CREB')-binding protein (CBP) modulates co-operation between myocyte enhancer factor 2A (MEF2A) and thyroid hormone receptor-retinoid X receptor

2003 ◽  
Vol 369 (3) ◽  
pp. 477-484 ◽  
Author(s):  
Antonio De LUCA ◽  
Anna SEVERINO ◽  
Paola De PAOLIS ◽  
Giuliano COTTONE ◽  
Luca De LUCA ◽  
...  
Keyword(s):  
Thyroid Hormone ◽  
Binding Protein ◽  
Camp Response Element Binding ◽  
Creb Binding Protein ◽  
Camp Response Element ◽  
Response Element ◽  
Adenovirus E1a ◽  
Element Binding Protein ◽  
Enhancer Factor

Thyroid hormone receptors (TRs) and members of the myocyte enhancer factor 2 (MEF2) family are involved in the regulation of muscle-specific gene expression during myogenesis. Physical interaction between these two factors is required to synergistically activate gene transcription. p300/cAMP-response-element-binding-protein ('CREB')-binding protein (CBP) interacting with transcription factors is able to increase their activity on target gene promoters. We investigated the role of p300 in regulating the TR—MEF2A complex. To this end, we mapped the regions of these proteins involved in physical interactions and we evaluated the expression of a chloramphenicol acetyltransferase (CAT) reporter gene in U2OS cells under control of the α-myosin heavy chain promoter containing the thyroid hormone response element (TRE). Our results suggested a role of p300/CBP in mediating the transactivation effects of the TR—retenoid X receptor (RxR)—MEF2A complex. Our findings showed that the same C-terminal portion of p300 binds the N-terminal domains of both TR and MEF2A, and our in vivo studies demonstrated that TR, MEF2A and p300 form a ternary complex. Moreover, by the use of CAT assays, we demonstrated that adenovirus E1A inhibits activation of transcription by TR—RxR—MEF2A—p300 but not by TR—RxR—MEF2A. Our data suggested that p300 can bind and modulate the activity of TR—RxR—MEF2A at TRE. In addition, it is speculated that p300 might modulate the activity of the TR—RxR—MEF2A complex by recruiting a hypothetical endogenous inhibitor which may act like adenovirus E1A.

scholarly journals Acetylation of cAMP-responsive Element-binding Protein (CREB) by CREB-binding Protein Enhances CREB-dependent Transcription

2003 ◽  
Vol 278 (18) ◽  
pp. 15727-15734 ◽  
Author(s):  
Qing Lu ◽  
Amanda E. Hutchins ◽  
Colleen M. Doyle ◽  
James R. Lundblad ◽  
Roland P. S. Kwok
Keyword(s):  
Binding Protein ◽  
Creb Binding Protein ◽  
Element Binding Protein ◽  
Responsive Element ◽  
Camp Responsive Element Binding
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