Implications of transcriptional coactivator CREB binding protein complexes in rheumatoid arthritis

The hormonal response of estrogen receptors (ER) α and ERβ is controlled by a number of cofactors, including the general transcriptional coactivator CREB-binding protein (CBP). Growing evidence suggests that specific kinase signaling events also modulate the formation and activity of the ER coactivation complex. Here we show that ERβ activity and target gene expression are decreased upon activation of ErbB2/ErbB3 receptors despite the presence of CBP. This inhibition of ERβ involved activation of the phosphatidylinositol 3-kinase/Akt pathway, abrogating the potential of CBP to facilitate ERβ response to estrogen. Such reduced activity was associated with an impaired ability of ERβ to recruit CBP upon activation of Akt. Mutation of serine 255, an Akt consensus site contained in the hinge region of ERβ, prevented the release of CBP and rendered ERβ transcriptionally more responsive to CBP coactivation, suggesting that Ser-255 may serve as a regulatory site to restrain ERβ activity in Akt-activated cells. In contrast, we found that CBP intrinsic activity was increased by Akt through threonine 1872, a consensus site for Akt in the cysteine- and histidine-rich 3 domain of CBP, indicating that such enhanced transcriptional potential of CBP did not serve to activate ERβ. Interestingly, nuclear receptors sharing a conserved Akt consensus site with ERβ also exhibit a reduced ability to be coactivated by CBP, whereas others missing that site were able to benefit from the activation of CBP by Akt. These results therefore outline a regulatory mechanism by which the phosphatidylinositol 3-kinase/Akt pathway may discriminate nuclear receptor response through coactivator transcriptional competence.

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CREB-binding protein gene, HAC701, negatively regulates WRKY45-dependent immunity in rice

10.1101/2020.08.26.268797 ◽

2020 ◽

Author(s):

Nino A. Espinas ◽

Tu Ngoc Le ◽

Miura Saori ◽

Yasuka Shimajiri ◽

Ken Shirasu ◽

...

Keyword(s):

Gene Expression ◽

Immune Responses ◽

Binding Protein ◽

Large Set ◽

Sequencing Analysis ◽

Creb Binding Protein ◽

Transcriptional Coactivator ◽

Wild Type ◽

Genome Wide ◽

H3k9 Acetylation

ABSTRACTCREB-binding protein (CBP) is a known transcriptional coactivator and an acetyltransferase that functions in several cellular processes by regulating gene expression. However, how it functions in plant immunity remains unexplored. By characterizing hac701, we demonstrate that HAC701 negatively regulates the immune responses in rice. hac701 shows enhanced disease resistance against a bacterial pathogen, Pseudomonas syringae pv. oryzae (Pso), which causes bacterial halo blight of rice. Our transcriptomic analysis revealed that rice WRKY45, one of the main regulators of rice immunity, is upregulated in hac701 and possibly conferring the resistance phenotype against Pso. The morphological phenotypes of hac701 single mutants were highly similar to WRKY45 overexpression transgenic lines reported in previous studies. In addition, we also compared the list of genes in these studies when WRKY45 is overexpressed and chemically induced transiently with the differentially expressed genes (DEGs) in hac701, and found that they largely overlap. When we investigated for cis-elements found 1kb upstream of WRKY45 gene and WRKY45-dependent DEGs, we found that WRKY45 promoter contains the CRE motif, a possible target of HAC701-mediated regulation. Genome-wide H3K9 acetylation profiling showed depletion of acetylation at large set of genes in hac701. However, consistent with the upregulation of WRKY45 gene expression, our ChIP-sequencing analysis demonstrated that regions of WRKY45 promoter are enriched in H3K9 acetylation in hac701 compared to the segregated wild type control in the mock condition. WRKY45 promoter might be on the receiving end for possible genome-wide compensatory effects when a global regulator like HAC701 is mutated. Finally, we show that HAC701 may have roles in systemic immune signaling. We therefore propose that wild type HAC701 negatively regulates WRKY45 gene expression, thereby suppressing immune responses.SIGNIFICANCEHAC701 is a member of CREB-binding protein (CBP) family that acts as transcriptional coactivator and acetyltransferase. However, little is known how it regulates innate immunity in plants. Herein we reported that rice HAC701 suppresses WRKY45-dependent defense pathway. Our study showed that HAC701 seemingly interacts genetically with WRKY45 in rice to modulate immune responses against pathogens.

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The Transcriptional Coactivator CREB-binding Protein Cooperates with STAT1 and NF-κB for Synergistic Transcriptional Activation of the CXC Ligand 9/Monokine Induced by Interferon-γ Gene

Journal of Biological Chemistry ◽

10.1074/jbc.m204544200 ◽

2002 ◽

Vol 278 (1) ◽

pp. 651-660 ◽

Cited By ~ 69

Author(s):

Miki Hiroi ◽

Yoshihiro Ohmori

Keyword(s):

Transcriptional Activation ◽

Binding Protein ◽

Interferon Γ ◽

Creb Binding Protein ◽

Transcriptional Coactivator

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Interaction of Human Immunodeficiency Virus Type 1 Tat with the Transcriptional Coactivators p300 and CREB Binding Protein

Journal of Virology ◽

10.1128/jvi.72.10.8252-8256.1998 ◽

1998 ◽

Vol 72 (10) ◽

pp. 8252-8256 ◽

Cited By ~ 139

Author(s):

Michael O. Hottiger ◽

Gary J. Nabel

Keyword(s):

Human Immunodeficiency Virus ◽

Human Immunodeficiency Virus Type ◽

Virus Type ◽

Rna Binding ◽

Binding Protein ◽

Creb Binding Protein ◽

Transcriptional Coactivator ◽

Immunodeficiency Virus ◽

Hiv 1

ABSTRACT Human immunodeficiency virus type 1 (HIV-1) encodes the transactivator protein Tat, which is essential for viral replication and progression to disease. Here we demonstrate that transcriptional activation by HIV-1 Tat involves p300 or the related cellular transcriptional coactivator CREB binding protein (CBP). Tat transactivation was inhibited by the 12S form of the adenovirus E1A gene product, which inhibits p300 function, and this inhibition was independent of its effect on NF-κB transcription. A biochemical interaction of p300 with Tat was demonstrated in vitro and in vivo by coimmunoprecipitation. The carboxy-terminal region of p300, which binds to E1A, was shown to bind specifically to the highly conserved basic domain of Tat, which also mediates binding to the Tat-responsive region RNA stem-loop structure. The ability of Tat to interact physically and functionally with this coactivator provides a mechanism to assemble a basal transcription complex which may subsequently respond to the effect of Tat on transcriptional elongation and represents a novel interaction between an RNA binding protein and a transcriptional coactivator.

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CBP, a transcriptional coactivator and acetyltransferase

Biochemistry and Cell Biology ◽

10.1139/o01-076 ◽

2001 ◽

Vol 79 (3) ◽

pp. 253-266 ◽

Cited By ~ 62

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.

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