CREB-binding Protein (CBP) p300 Enhanced the Expression of Cardiac Hypertrophy-Specific Genes Activated by Myocardin-Related Transcription Factor-A (MRTF-A)

2012 ◽  
Author(s):  
Mingzhe Li ◽  
Zhenyu Wang ◽  
Zhongyi Xie ◽  
Jing Luo ◽  
Dongsun Cao ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Cardiac Hypertrophy ◽  
Binding Protein ◽  
Creb Binding Protein ◽  
Related Transcription Factor

scholarly journals Regulation of Transcription by Hypoxia Requires a Multiprotein Complex That Includes Hypoxia-Inducible Factor 1, an Adjacent Transcription Factor, and p300/CREB Binding Protein

1998 ◽  
Vol 18 (7) ◽  
pp. 4089-4096 ◽  
Author(s):  
Benjamin L. Ebert ◽  
H. Franklin Bunn
Keyword(s):  
Transcription Factor ◽  
Transcription Factors ◽  
Dna Binding ◽  
Binding Proteins ◽  
Binding Protein ◽  
Hypoxia Inducible Factor ◽  
Dna Binding Proteins ◽  
Creb Binding Protein ◽  
Multiprotein Complex ◽  
Hypoxia Inducible Factor 1

ABSTRACT Molecular adaptation to hypoxia depends on the binding of hypoxia-inducible factor 1 (HIF-1) to cognate response elements in oxygen-regulated genes. In addition, adjacent sequences are required for hypoxia-inducible transcription. To investigate the mechanism of interaction between these cis-acting sequences, the multiprotein complex binding to the lactate dehydrogenase A (LDH-A) promoter was characterized. The involvement of HIF-1, CREB-1/ATF-1, and p300/CREB binding protein (CBP) was demonstrated by techniques documenting in vitro binding, in combination with transient transfections that test the in vivo functional importance of each protein. In both the LDH-A promoter and the erythropoietin 3′ enhancer, formation of multiprotein complexes was analyzed by using biotinylated probes encompassing functionally critical cis-acting sequences. Strong binding of p300/CBP required interactions with multiple DNA binding proteins. Thus, the necessity of transcription factor binding sites adjacent to a HIF-1 site for hypoxically inducible transcription may be due to the requirement of p300 to interact with multiple transcription factors for high-affinity binding and activation of transcription. Since it has been found to interact with a wide range of transcription factors, p300 is likely to play a similar role in other genes, mediating interactions between DNA binding proteins, thereby activating stimulus-specific and tissue-specific gene transcription.

scholarly journals Regulatory domains of the A-Myb transcription factor and its interaction with the CBP/p300 adaptor molecules

1997 ◽  
Vol 324 (3) ◽  
pp. 729-736 ◽  
Author(s):  
Valeria FACCHINETTI ◽  
Livio LOFFARELLI ◽  
Sabine SCHREEK ◽  
Michael OELGESCHLÄGER ◽  
Bernhard LÜSCHER ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Dna Binding ◽  
Binding Protein ◽  
Camp Response Element Binding ◽  
Binding Activity ◽  
Myb Transcription Factor ◽  
Physical Interaction ◽  
Creb Binding Protein ◽  
Activation Domain ◽  
Activation Potential

The A-Myb transcription factor belongs to the Myb family of oncoproteins and is likely to be involved in the regulation of proliferation and/or differentiation of normal B cells and Burkitt's lymphoma cells. To characterize in detail the domains of A-Myb that regulate its function, we have generated a series of deletion mutants and have investigated their trans-activation potential as well as their DNA-binding activity. Our results have allowed us to delineate the trans-activation domain as well as two separate regulatory regions. The boundaries of the trans-activation domain (amino acid residues 218–319) are centred on a sequence rich in charged amino acids (residues 259–281). A region (residues 320–482) localized immediately downstream of the trans-activation domain and containing a newly identified conserved stretch of 48 residues markedly inhibits specific DNA binding. Finally the last 110 residues of A-Myb (residues 643–752), which include a sequence conserved in all mammalian myb genes (region III), negatively regulate the maximal trans-activation potential of A-Myb. We have also investigated the functional interaction between A-Myb and the nuclear adaptor molecule CBP [cAMP response element-binding protein (CREB)-binding protein]. We demonstrate that CBP synergizes with A-Myb in a dose-dependent fashion, and that this co-operative effect can be inhibited by E1A and can also be observed with the CBP homologue p300. We show that this functional synergism requires the presence of the A-Myb charged sequence and that it involves physical interaction between A-Myb and the CREB-binding domain of CBP.

scholarly journals Non-Canonical Activation of CREB Mediates Neuroprotection in a C. elegans Model of Excitotoxic Necrosis

2018 ◽  
Author(s):  
K. Genevieve Feldmann ◽  
Ayesha Chowdhury ◽  
Jessi Becker ◽  
N’Gina McAlpin ◽  
Taqwa Ahmed ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Transcriptional Activation ◽  
Binding Protein ◽  
Neuroprotective Effect ◽  
Camp Response Element Binding ◽  
Creb Binding Protein ◽  
Creb Phosphorylation ◽  
C Elegans ◽  
Creb Activation ◽  
Specific Subset

AbstractExcitotoxicity, caused by exaggerated neuronal stimulation by Glutamate (Glu), is a major cause of neurodegeneration in brain ischemia. While we know that neurodegeneration is triggered by overstimulation of Glu-Receptors (GluRs), the subsequent mechanisms that lead to cellular demise remain controversial. Surprisingly, signaling downstream of GluRs can also activate neuroprotective pathways. The strongest evidence involves activation of the transcription factor cAMP Response Element Binding-protein (CREB), widely recognized for its importance in synaptic plasticity. Canonical views describe CREB as a phosphorylation-triggered transcription factor, where transcriptional activation involves CREB phosphorylation and association with CREB Binding Protein (CBP). However, given CREB’s ubiquitous cross-tissue expression, the multitude of cascades leading to CREB phosphorylation, and its ability to regulate thousands of genes, it remains unclear how CREB exerts closely-tailored, differential neuroprotective responses in excitotoxicity. A non-canonical, alternative cascade for activation of CREB-mediated transcription involves the CREB co-factor cAMP-regulated transcriptional co-activator (CRTC), and may be independent of CREB phosphorylation. To identify cascades that activate CREB in excitotoxicity we use a C. elegans model of neurodegeneration by excitotoxic necrosis. We demonstrate that CREB’s neuroprotective effect is conserved, and seems most effective in neurons with moderate Glu exposure. We find that factors mediating canonical CREB activation are not involved. Instead, phosphorylation-independent CREB activation in nematode excitotoxic necrosis hinges on CRTC. CREB-mediated transcription that depends on CRTC, but not on CREB phosphorylation, might lead to expression of a specific subset of neuroprotective genes. Elucidating conserved mechanisms of excitotoxicity-specific CREB activation can help us focus on core neuroprotective programs in excitotoxicity.

scholarly journals Cooperativity in Transcription Factor Binding to the Coactivator CREB-binding Protein (CBP)

2002 ◽  
Vol 277 (45) ◽  
pp. 43168-43174 ◽  
Author(s):  
Natalie K. Goto ◽  
Tsaffrir Zor ◽  
Maria Martinez-Yamout ◽  
H. Jane Dyson ◽  
Peter E. Wright
Keyword(s):  
Transcription Factor ◽  
Binding Protein ◽  
Transcription Factor Binding ◽  
Creb Binding Protein ◽  
Factor Binding

scholarly journals Mapping the Promiscuous Binding Interface of HOX-A11 with KIX by Experimentally Guided in-silico docking

2021 ◽  
Author(s):  
Soumya Ganguly ◽  
Günter P. Wagner ◽  
Jens Meiler
Keyword(s):  
Transcription Factor ◽  
Protein Interactions ◽  
Binding Protein ◽  
Creb Binding Protein ◽  
Computational Docking ◽  
In Silico Docking ◽  
Intrinsically Disordered ◽  
Intrinsically Disordered Regions ◽  
Binding Interface ◽  
Kix Domain

AbstractTranscription factors (TFs) regulate levels of transcription through a complex array of protein-protein interactions, thereby controlling key physiological processes such as development, stress response and cell growth. The transcription factor HOXA11 contains an intrinsically disordered regions (IDR) through which it interacts with CREB binding protein (CBP) and regulates endometrial development and function in eutherian mammals. The interaction between the IDR of HOXA11 and CBP was analyzed using computational docking guided by experimental constraints. HOXA11 IDR interacts with the KIX domain of CBP at two discrete sites – MLL and cMyb, mediated by sticky hydrophobic grooves on the surface of KIX. A five residue motif FDQFF on HOXA11 can interact both at cMyb and MLL site of KIX resulting in a promiscuous binding.Author SummaryWe demonstrate how the intrinsically disordered region (IDR) of transcription factor HOXA11 interacts at two distinct sites of the transcription coactivator CREB binding protein (CBP). By combining computational docking with limited experimental data we construct models of the complex of the KIX domain within CBP and a short helical segment within the IDR of HOXA11. The interaction between HOXA11 and CBP is believed to trigger the downstream expression of genes important in embryonic development.

scholarly journals Recruitment of CREB Binding Protein Is Sufficient for CREB-Mediated Gene Activation

2000 ◽  
Vol 20 (5) ◽  
pp. 1546-1552 ◽  
Author(s):  
Jean-Rene Cardinaux ◽  
John C. Notis ◽  
Qinghong Zhang ◽  
Ngan Vo ◽  
Johanna C. Craig ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Transcriptional Activation ◽  
Binding Protein ◽  
Gene Activation ◽  
Activation Process ◽  
Creb Binding Protein ◽  
Protein Protein Interaction ◽  
Binding Domains ◽  
Phosphorylation Event ◽  
Element Binding Protein

ABSTRACT Phosphorylation of the transcription factor CREB leads to the recruitment of the coactivator, CREB binding protein (CBP). Recent studies have suggested that CBP recruitment is not sufficient for CREB function, however. We have identified a conserved protein-protein interaction motif within the CBP-binding domains of CREB and another transcription factor, SREBP (sterol-responsive element binding protein). In contrast to CREB, SREBP interacts with CBP in the absence of phosphorylation. We have exploited the conservation of this interaction motif to test whether CBP recruitment to CREB is sufficient for transcriptional activation. Substitution of six nonconserved amino acids from SREBP into the activation domain of CREB confers high-affinity, phosphorylation-independent CBP binding. The mutated CREB molecule, CREBDIEDML, activates transcription in F9 teratocarcinoma and PC12 cells even in the absence of protein kinase A (PKA). Addition of exogenous CBP augments the level of transcription mediated by CREBDIEDML, and adenovirus 12S E1A blocks transcription, implicating CBP in the activation process. Thus, recruitment of CBP to CREB is sufficient for transcriptional activation. Addition of PKA stimulates transcription induced by CREBDIEDML further, suggesting that a phosphorylation event downstream from CBP recruitment augments CREB signaling.

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