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Shoumo Bhattacharya - One of the best experts on this subject based on the ideXlab platform.
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human creb binding Protein p300 interacting transactivator with ed rich tail cited 4 a new member of the cited family functions as a co activator for transcription factor ap 2
Journal of Biological Chemistry, 2002Co-Authors: Jose Braganca, Tracey Swingler, Fatima I R Marques, Tania A Jones, Jyrki J Eloranta, Helen C Hurst, Toshihiro Shioda, Shoumo BhattacharyaAbstract:Abstract Members of the CREB-binding Protein/p300-interacting transactivator with ED-rich tail (CITED) family bind CREB-binding Protein and p300 with high affinity and regulate gene transcription. Gene knockout studies indicate that CITED2 is required for neural crest and neural tube development and that it functions as a co-activator for transcription factor AP-2 (TFAP2). Here we describe human CITED4, a new member of this family, which is encoded by a single exon mapping to chromosome 1p34–1p35. CITED4 and p300/CREB-binding Protein are present in endogenous naturally occurring complexes, indicating that they interact physiologically. The interaction occurs between the cysteine-histidine-rich domain 1 of p300 and the carboxyl terminus of CITED4. In keeping with this, CITED4 functions as a transactivator when artificially targeted to a promoter element. CITED4 physically interacts with all TFAP2 isoforms in vitro and strongly co-activates all TFAP2 isoforms in Hep3B cells. Co-activation of TFAP2 requires amino-terminal and carboxyl-terminal residues of CITED4. In HepG2 cells, CITED4 is significantly weaker than CITED2 for TFAP2C co-activation. These results suggest that CITED4 may function as a co-activator for TFAP2. They also suggest the existence of cell type- and TFAP2 isoform-specific co-activation by CITED2 and CITED4, which may result in differential modulation of TFAP2 function.
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Human CREB-binding Protein/p300-interacting Transactivator with ED-rich Tail (CITED) 4, a New Member of the CITED Family, Functions as a Co-activator for Transcription Factor AP-2 *
The Journal of biological chemistry, 2001Co-Authors: Jose Braganca, Tracey Swingler, Fatima I R Marques, Tania A Jones, Jyrki J Eloranta, Helen C Hurst, Toshihiro Shioda, Shoumo BhattacharyaAbstract:Members of the CREB-binding Protein/p300-interacting transactivator with ED-rich tail (CITED) family bind CREB-binding Protein and p300 with high affinity and regulate gene transcription. Gene knockout studies indicate that CITED2 is required for neural crest and neural tube development and that it functions as a co-activator for transcription factor AP-2 (TFAP2). Here we describe human CITED4, a new member of this family, which is encoded by a single exon mapping to chromosome 1p34--1p35. CITED4 and p300/CREB-binding Protein are present in endogenous naturally occurring complexes, indicating that they interact physiologically. The interaction occurs between the cysteine-histidine-rich domain 1 of p300 and the carboxyl terminus of CITED4. In keeping with this, CITED4 functions as a transactivator when artificially targeted to a promoter element. CITED4 physically interacts with all TFAP2 isoforms in vitro and strongly co-activates all TFAP2 isoforms in Hep3B cells. Co-activation of TFAP2 requires amino-terminal and carboxyl-terminal residues of CITED4. In HepG2 cells, CITED4 is significantly weaker than CITED2 for TFAP2C co-activation. These results suggest that CITED4 may function as a co-activator for TFAP2. They also suggest the existence of cell type- and TFAP2 isoform-specific co-activation by CITED2 and CITED4, which may result in differential modulation of TFAP2 function.
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Localization of human CREB-binding Protein gene (CREBBP) to 16p13.2-p13.3 by fluorescence in situ hybridization.
Genomics, 1995Co-Authors: K. L. Wydner, Shoumo Bhattacharya, Richard Eckner, Jeanne B. Lawrence, David M. LivingstonAbstract:The adenovirus E1a oncoProtein targets a number of negative regulators of cellular proliferation, including the retinoblastoma gene product RB, p107, p130, p300, and the CREB-binding Protein (CBP). p300 and CBP are highly homologous Proteins that are thought to function as transcriptional coactivators, with roles in the regulation of the cell cycle and in cell differentiation. Like the RB Protein, these Proteins also may function as tumor suppressors. We have mapped the chromosomal location of the human CBP gene 3 as a first step in defining its possible involvement in human neoplasia. 11 refs.
Jose Braganca - One of the best experts on this subject based on the ideXlab platform.
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human creb binding Protein p300 interacting transactivator with ed rich tail cited 4 a new member of the cited family functions as a co activator for transcription factor ap 2
Journal of Biological Chemistry, 2002Co-Authors: Jose Braganca, Tracey Swingler, Fatima I R Marques, Tania A Jones, Jyrki J Eloranta, Helen C Hurst, Toshihiro Shioda, Shoumo BhattacharyaAbstract:Abstract Members of the CREB-binding Protein/p300-interacting transactivator with ED-rich tail (CITED) family bind CREB-binding Protein and p300 with high affinity and regulate gene transcription. Gene knockout studies indicate that CITED2 is required for neural crest and neural tube development and that it functions as a co-activator for transcription factor AP-2 (TFAP2). Here we describe human CITED4, a new member of this family, which is encoded by a single exon mapping to chromosome 1p34–1p35. CITED4 and p300/CREB-binding Protein are present in endogenous naturally occurring complexes, indicating that they interact physiologically. The interaction occurs between the cysteine-histidine-rich domain 1 of p300 and the carboxyl terminus of CITED4. In keeping with this, CITED4 functions as a transactivator when artificially targeted to a promoter element. CITED4 physically interacts with all TFAP2 isoforms in vitro and strongly co-activates all TFAP2 isoforms in Hep3B cells. Co-activation of TFAP2 requires amino-terminal and carboxyl-terminal residues of CITED4. In HepG2 cells, CITED4 is significantly weaker than CITED2 for TFAP2C co-activation. These results suggest that CITED4 may function as a co-activator for TFAP2. They also suggest the existence of cell type- and TFAP2 isoform-specific co-activation by CITED2 and CITED4, which may result in differential modulation of TFAP2 function.
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Human CREB-binding Protein/p300-interacting Transactivator with ED-rich Tail (CITED) 4, a New Member of the CITED Family, Functions as a Co-activator for Transcription Factor AP-2 *
The Journal of biological chemistry, 2001Co-Authors: Jose Braganca, Tracey Swingler, Fatima I R Marques, Tania A Jones, Jyrki J Eloranta, Helen C Hurst, Toshihiro Shioda, Shoumo BhattacharyaAbstract:Members of the CREB-binding Protein/p300-interacting transactivator with ED-rich tail (CITED) family bind CREB-binding Protein and p300 with high affinity and regulate gene transcription. Gene knockout studies indicate that CITED2 is required for neural crest and neural tube development and that it functions as a co-activator for transcription factor AP-2 (TFAP2). Here we describe human CITED4, a new member of this family, which is encoded by a single exon mapping to chromosome 1p34--1p35. CITED4 and p300/CREB-binding Protein are present in endogenous naturally occurring complexes, indicating that they interact physiologically. The interaction occurs between the cysteine-histidine-rich domain 1 of p300 and the carboxyl terminus of CITED4. In keeping with this, CITED4 functions as a transactivator when artificially targeted to a promoter element. CITED4 physically interacts with all TFAP2 isoforms in vitro and strongly co-activates all TFAP2 isoforms in Hep3B cells. Co-activation of TFAP2 requires amino-terminal and carboxyl-terminal residues of CITED4. In HepG2 cells, CITED4 is significantly weaker than CITED2 for TFAP2C co-activation. These results suggest that CITED4 may function as a co-activator for TFAP2. They also suggest the existence of cell type- and TFAP2 isoform-specific co-activation by CITED2 and CITED4, which may result in differential modulation of TFAP2 function.
Annick Harel-bellan - One of the best experts on this subject based on the ideXlab platform.
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CREB-binding Protein/p300 activates MyoD by acetylation.
The Journal of biological chemistry, 2000Co-Authors: Anna Polesskaya, Arnaud Duquet, Eyal Bengal, Irina Naguibneva, Christoph Weise, Arlette Vervisch, Ferdinand Hucho, Philippe Robin, Annick Harel-bellanAbstract:The myogenic Protein MyoD requires two nuclear histone acetyltransferases, CREB-binding Protein (CBP)/p300 and PCAF, to transactivate muscle promoters. MyoD is acetylated by PCAF in vitro, which seems to increase its affinity for DNA. We here show that MyoD is constitutively acetylated in muscle cells. In vitro, MyoD is acetylated both by CBP/p300 and by PCAF on two lysines located at the boundary of the DNA binding domain. MyoD acetylation by CBP/p300 (as well as by PCAF) increases its activity on a muscle-specific promoter, as assessed by microinjection experiments. MyoD mutants that cannot be acetylated in vitro are not activated in the functional assay. Our results provide direct evidence that MyoD acetylation functionally activates the Protein and show that both PCAF and CBP/p300 are candidate enzymes for MyoD acetylation in vivo.
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The CREB-binding Protein (CBP) cooperates with the serum response factor for transactivation of the c-fos serum response element.
The Journal of biological chemistry, 1997Co-Authors: Sandra Ramirez, Philippe Robin, Slimane Ait Si Ali, Didier Trouche, Annick Harel-bellanAbstract:The serum response element is one of the major promoter elements of the immediate early response to extracellular signals. The serum response element includes two main binding sites for Proteins: the Ets box, which binds p62(TCF), and the CArG box, which binds p67(SRF). These two Proteins are direct targets for signal transduction pathways; p62(TCF) is a nuclear end point of the Ras/mitogen-activated Protein kinase pathway, and p67(SRF) is targeted by the Rho/Rac small G-Proteins. The mechanism by which the signal is further transduced from the transcription factors to the basal transcriptional machinery is poorly understood. Recent data have suggested that the cAMP-responsive element-binding Protein (CREB)-binding Protein, a transcriptional adaptor involved in the transactivation through a wide variety of enhancer elements, participates in p62(TCF) activity. We here show that the CREB-binding Protein also cooperates in the process of transactivation by p67(SRF). Cotransfections of expression vectors for the CREB-binding Protein increased the expression, in response to serum, of reporters under the control of the c-fos serum response element. Interestingly, the C-terminal moiety of the CREB-binding Protein was not necessary to observe this effect. The cooperation did not require the Ets box in the serum response element, and the CArG box was sufficient, indicating that the CREB-binding Protein is able to cooperate with p67(SRF) in the absence of an Ets Protein. Co-immunoprecipitation experiments using cell extracts showed that p67(SRF) could be retained with antibodies directed against the CREB-binding Protein, suggesting that the two Proteins form a multimolecular complex in live cells. The physical interaction between p67(SRF) and the CREB-binding Protein was further confirmed by two-hybrid assays in mammalian cells. Our results indicate that the CREB-binding Protein cooperates with p67(SRF) and, thus, suggest that the serum response element is regulated by a multimolecular complex, which includes the CREB-binding Protein, p67(SRF), and p62(TCF), with multiple interactions between the components of the complex.
Toshihiro Nakajima - One of the best experts on this subject based on the ideXlab platform.
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Implications of transcriptional coactivator CREB binding Protein complexes in rheumatoid arthritis.
Modern rheumatology, 2004Co-Authors: Toshihiro Nakajima, Satoko Aratani, Minako Nakazawa, Takuji Hirose, Hidetoshi Fujita, Kusuki NishiokaAbstract:Transcriptional coactivators have crucial roles in eukaryotic transcription. It has been suggested that one of the coactivators, cAMP response element binding Protein (CREB) binding Protein (CBP), regulates gene expression with a number of transcription factors via two mechanisms. One is the recruitment of general transcriptional machinery to the promoters. The other is its intrinsic and associated histone acetyltransferase (HAT) activity, which increases the accessibility of the activator to DNA, and the acetylation of nonhistone Proteins. Rheumatoid arthritis (RA) is characterized by the inflammation and proliferation of synovium, leading to the destruction of articular cartilage and bone. To understand the pathogenesis of RA, we focused the transcription mechanism through CBP in synoviocytes and chondrocytes. We identified Notch-1 in synoviocytes and p34SEI-1 in chondrocytes as CBP binding Proteins by yeast two-hybrid screening. It was also suggested that the acetylation of p53 could repress transactivation in RA synoviocytes. These associations may regulate proliferation and apoptosis. This study suggests that regulation of the coactivator could become a novel strategy for RA therapy.
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the autoimmune regulator Protein has transcriptional transactivating properties and interacts with the common coactivator creb binding Protein
Journal of Biological Chemistry, 2000Co-Authors: Jukka Pitkanen, Perttu Vahamurto, Vassilis Doucas, Kirsten Jensen, Satoko Aratani, Thomas Sternsdorf, Hans Will, Toshihiro Nakajima, Juha OllilaAbstract:Autoimmune polyendocrinopathy candidiasis ectodermal dystrophy, caused by mutations in the autoimmune regulator (AIRE) gene, is an autosomal recessive autoimmune disease characterized by the breakdown of tolerance to organ-specific antigens. The 545 amino acid Protein encoded by AIRE contains several structural motifs suggestive of a transcriptional regulator and bears similarity to cellular Proteins involved in transcriptional control. me show here that AIRE fused to a heterologous DNA binding domain activates transcription from a reporter promoter, and the activation seen requires the full-length Protein or more than one activation domain. At the structural level AIRE forms homodimers through the NH2-terminal domain, and molecular modeling for this domain suggests a four-helix bundle structure. In agreement, we show that the common transcriptional coactivator CREB-binding Protein (CBP) interacts with AIRE in vitro and in yeast nuclei through the CH1 and CH3 conserved domains. We suggest that the transcriptional transactivation properties of AIRE together with its interaction with CBP might be important in its function as disease-causing mutations almost totally abolish the activation effect. (Less)
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The autoimmune regulator Protein has transcriptional transactivating properties and interacts with the common coactivator CREB-binding Protein.
The Journal of biological chemistry, 2000Co-Authors: Jukka Pitkanen, Perttu Vahamurto, Vassilis Doucas, Juha Ollila, Kirsten Jensen, Satoko Aratani, Thomas Sternsdorf, Hans Will, Toshihiro Nakajima, Mauno VihinenAbstract:Autoimmune polyendocrinopathy candidiasis ectodermal dystrophy, caused by mutations in the autoimmune regulator (AIRE) gene, is an autosomal recessive autoimmune disease characterized by the breakdown of tolerance to organ-specific antigens. The 545 amino acid Protein encoded by AIRE contains several structural motifs suggestive of a transcriptional regulator and bears similarity to cellular Proteins involved in transcriptional control. We show here that AIRE fused to a heterologous DNA binding domain activates transcription from a reporter promoter, and the activation seen requires the full-length Protein or more than one activation domain. At the structural level AIRE forms homodimers through the NH(2)-terminal domain, and molecular modeling for this domain suggests a four-helix bundle structure. In agreement, we show that the common transcriptional coactivator CREB-binding Protein (CBP) interacts with AIRE in vitro and in yeast nuclei through the CH1 and CH3 conserved domains. We suggest that the transcriptional transactivation properties of AIRE together with its interaction with CBP might be important in its function as disease-causing mutations almost totally abolish the activation effect.
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CREB-binding Protein cooperates with transcription factor GATA-1 and is required for erythroid differentiation
Proceedings of the National Academy of Sciences of the United States of America, 1998Co-Authors: Gerd A. Blobel, Toshihiro Nakajima, Richard Eckner, Marc Montminy, Stuart H. OrkinAbstract:The transcription factor GATA-1 coordinates multiple events during terminal erythroid cell maturation. GATA-1 participates in the transcription of virtually all erythroid-specific genes, blocks apoptosis of precursor cells, and controls the balance between proliferation and cell cycle arrest. Prior studies suggest that the function of GATA-1 is mediated in part through association with transcriptional cofactors. CREB-binding Protein (CBP) and its close relative p300 serve as coactivators for a variety of transcription factors involved in growth control and differentiation. We report here that CBP markedly stimulates GATA-1’s transcriptional activity in transient transfection experiments in nonhematopoietic cells. GATA-1 and CBP also coimmunoprecipitate from nuclear extracts of erythroid cells. Interaction mapping pinpoints contact sites to the zinc finger region of GATA-1 and to the E1A-binding region of CBP. Expression of a conditional form of adenovirus E1A in murine erythroleukemia cells blocks differentiation and expression of endogenous GATA-1 target genes, whereas mutant forms of E1A unable to bind CBP/p300 have no effect. Our findings add GATA-1, and very likely other members of the GATA family, to the growing list of molecules implicated in the complex regulatory network surrounding CBP/p300.
Peter E. Wright - One of the best experts on this subject based on the ideXlab platform.
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Role of Backbone Dynamics in Modulating the Interactions of Disordered Ligands with the TAZ1 Domain of the CREB-binding Protein
Biochemistry, 2019Co-Authors: Rebecca B. Berlow, H. Jane Dyson, Maria A. Martinez-yamout, Peter E. WrightAbstract:The intrinsically disordered transactivation domains of HIF-1α and CITED2 compete for binding of the TAZ1 domain of the CREB-binding Protein by a unidirectional allosteric mechanism involving direct competition for shared binding sites, ternary complex formation, and TAZ1 conformational changes. To gain insight into the mechanism by which CITED2 displaces HIF-1α from TAZ1, we used nuclear magnetic resonance spin relaxation methods to obtain an atomic-level description of the picosecond to nanosecond backbone dynamics that contribute to TAZ1 binding and competition. We show that HIF-1α and CITED2 adopt different dynamics in their complexes with TAZ1, with flexibility observed for HIF-1α in regions that would maintain accessibility for CITED2 to bind to TAZ1 and facilitate subsequent HIF-1α dissociation. In contrast, critical regions of CITED2 adopt a rigid structure in its complex with TAZ1, minimizing the ability of HIF-1α to compete for binding. We also find that TAZ1, previously thought to be a rigid sc...
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Role of Intrinsic Protein Disorder in the Function and Interactions of the Transcriptional Coactivators CREB-binding Protein (CBP) and p300 *
The Journal of biological chemistry, 2016Co-Authors: H.j. Dyson, Peter E. WrightAbstract:The transcriptional coactivators CREB-binding Protein (CBP) and p300 undergo a particularly rich set of interactions with disordered and partly ordered partners, as a part of their ubiquitous role in facilitating transcription of genes. CBP and p300 contain a number of small structured domains that provide scaffolds for the interaction of disordered transactivation domains from a wide variety of partners, including p53, hypoxia-inducible factor 1α (HIF-1α), NF-κB, and STAT Proteins, and are the targets for the interactions of disordered viral Proteins that compete with cellular factors to disrupt signaling and subvert the cell cycle. The functional diversity of the CBP/p300 interactome provides an excellent example of the power of intrinsic disorder to facilitate the complexity of living systems.
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Graded enhancement of p53 binding to CREB-binding Protein (CBP) by multisite phosphorylation
Proceedings of the National Academy of Sciences of the United States of America, 2010Co-Authors: Chul Won Lee, Josephine C. Ferreon, Allan Chris M. Ferreon, Munehito Arai, Peter E. WrightAbstract:The transcriptional activity of p53 is regulated by a cascade of posttranslational modifications. Although acetylation of p53 by CREB-binding Protein (CBP)/p300 is known to be indispensable for p53 activation, the role of phosphorylation, and in particular multisite phosphorylation, in activation of CBP/p300-dependent p53 transcriptional pathways remains unclear. We investigated the role of single site and multiple site phosphorylation of the p53 transactivation domain in mediating its interaction with CBP and with the ubiquitin ligase HDM2. Phosphorylation at Thr18 functions as an on/off switch to regulate binding to the N-terminal domain of HDM2. In contrast, binding to CBP is modulated by the extent of p53 phosphorylation; addition of successive phosphoryl groups enhances the affinity for the TAZ1, TAZ2, and KIX domains of CBP in an additive manner. Activation of p53-dependent transcriptional pathways requires that p53 compete with numerous cellular transcription factors for binding to limiting amounts of CBP/p300. Multisite phosphorylation represents a mechanism for a graded p53 response, with each successive phosphorylation event resulting in increasingly efficient recruitment of CBP/p300 to p53-regulated transcriptional programs, in the face of competition from cellular transcription factors. Multisite phosphorylation thus acts as a rheostat to enhance binding to CBP/p300 and provides a plausible mechanistic explanation for the gradually increasing p53 response observed following prolonged or severe genotoxic stress.
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Packing, specificity, and mutability at the binding interface between the p160 coactivator and CREB-binding Protein.
Protein science : a publication of the Protein Society, 2004Co-Authors: Stephen J. Demarest, Ronald M. Evans, Songpon Deechongkit, H. Jane Dyson, Peter E. WrightAbstract:Among the most common interaction motifs between nuclear Proteins is the recognition of one or more amphipathic helices. In an effort to determine principles behind this recognition, we have investigated the interaction between the p160 coactivator Protein ACTR and the ACTR-binding domain of the CREB-binding Protein, CBP. The two Proteins use relatively small portions of their primary sequences to form a single synergistically folded domain consisting of six intertwined alpha-helices, three from each Protein. Neither of the component polypeptides forms a cooperatively folded domain in isolation. However, a considerable amount of residual secondary structure remains in the isolated CBP domain according to CD spectroscopy. Chemical denaturation, differential scanning calorimetry, and ANS binding experiments demonstrate that the isolated CBP domain is not entirely unfolded but forms a helical state with the characteristics of a molten globule. Mutations probing the functional and energetic significance of a buried intermolecular Arg-Asp salt bridge in the interface of the Protein complex suggest that these residues are tuned for functional discrimination and not strictly for binding affinity or stability. These results suggest a mechanism for formation of the complex where the unfolded ACTR domain interacts with the partly folded CBP domain in a rapid and specific manner to form the final stable complex.