Distinct cAMP response element-binding protein (CREB) domains stimulate different steps in a concerted mechanism of transcription activation

Kim, Jeong‐A; Lü, Jing-Fang; Quinn, Patrick G.

doi:10.1073/pnas.97.21.11292

Cited by 23 publications

(21 citation statements)

References 46 publications

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“…Furthermore, these findings support the notion that different classes of activation domains can be divided into groups that influence distinct steps of the transcription process, i.e., recruitment of chromatin-remodeling activities, recruitment of basal transcription factors, recruitment of coactivators, enhancement of initiation and reinitiation rates, transcription elongation, and RNA processing. Consistent with this, Kim et al have characterized the two activation domains of CREB (cyclic AMP-responsive element-binding protein) and found that the constitutive activation domain is required for preinitiation complex formation and the induced activation domain is required for multiple rounds of transcription (14).…”

Section: Vol 22 2002 Mechanism Of Rapid Induction Of Nf-b Target Gementioning

confidence: 64%

Mechanism of Rapid Transcriptional Induction of Tumor Necrosis Factor Alpha-Responsive Genes by NF-κB

Ainbinder

Revach

Wolstein

et al. 2002

Molecular and Cellular Biology

109

101

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NF-B induces the expression of genes involved in immune response, apoptosis, inflammation, and the cell cycle. Certain NF-B-responsive genes are activated rapidly after the cell is stimulated by cytokines and other extracellular signals. However, the mechanism by which these genes are activated is not entirely understood. Here we report that even though NF-B interacts directly with TAF II s, induction of NF-B by tumor necrosis factor alpha (TNF-␣) does not enhance TFIID recruitment and preinitiation complex formation on some NF-B-responsive promoters. These promoters are bound by the transcription apparatus prior to TNF-␣ stimulus. Using the immediate-early TNF-␣-responsive gene A20 as a prototype promoter, we found that the constitutive association of the general transcription apparatus is mediated by Sp1 and that this is crucial for rapid transcriptional induction by NF-B. In vitro transcription assays confirmed that NF-B plays a postinitiation role since it enhances the transcription reinitiation rate whereas Sp1 is required for the initiation step. Thus, the consecutive effects of Sp1 and NF-B on the transcription process underlie the mechanism of their synergy and allow rapid transcriptional induction in response to cytokines.The family of NF-B transcription factors is a central component of the cellular response to a broad range of extracellular signals, many of them are related to immunological functions and stress. NF-B controls the expression of a large number of genes including inflammatory cytokines, chemokines, immunological factors, adhesion molecules, cell cycle regulators, and pro-and antiapoptotic factors (24). A major pathway regulating NF-B activity involves its nuclear transport. In unstimulated cells, NF-B is retained in the cytoplasm in an inactive form by IB proteins. Signals that activate NF-B trigger ubiquitination and degradation of IB by the proteosome, resulting in transport of NF-B into the nucleus and transcriptional activation of responsive genes. Since IB␣ is one of the NF-B target genes, the newly synthesized IB␣ negatively regulates NF-B, thus forming an autoregulatory loop.In the nucleus, transcriptional activation by NF-B involves its association with multiple coactivators. We reported previously that the substoichiometric TFIID subunit, TAF II 105, which is enriched in B cells, interacts directly with p65/Re1A, a member of the NF-B family, and is important for activation of a subset of NF-B-dependent antiapoptotic genes in vivo (30,36,37). Likewise, other TFIID subunits such as hTAF II 250, hTAF II 80, and hTAF II 28 were reported to bind to p65/Re1A (8), although the physiological importance of these interactions was not investigated. In addition to TFIID, the coactivator protein CREB-binding protein CBP and its homolog p300 were reported to be involved in transcription activation by the p65/Re1A subunit of NF-B (6, 25). p65 was also found to interact specifically with the composite coactivator ARC/DRIP, and this complex supports NF-B-dependent transcriptional activation in v...

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Section: Vol 22 2002 Mechanism Of Rapid Induction Of Nf-b Target Gementioning

confidence: 64%

Mechanism of Rapid Transcriptional Induction of Tumor Necrosis Factor Alpha-Responsive Genes by NF-κB

Ainbinder

Revach

Wolstein

et al. 2002

Molecular and Cellular Biology

109

101

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“…Interestingly, CREB can stimulate both basal transcription and inducible transcription through its bipartite transcriptional activation domain [34,38,39]. The domain contains a constitutive activation domain that can interact with components of the general transcriptional machinery and a kinase-inducible domain that when phosphorylated at a serine residue promotes the recruitment of transcriptional co-activators such as CREB-binding protein and p300 [38][39][40][41][42][43]. A recent study of CREB binding has shown that the protein has the ability to bind its cognate site in responsive gene promotes either as a monomer or as a homodimer or a heterodimer with other transcription factors such as NFIL3 [44].…”

Section: Discussionmentioning

confidence: 99%

Regulation of the human SOX9 promoter by Sp1 and CREB

Piera-Velázquez

Hawkins

Whitecavage

et al. 2007

Experimental Cell Research

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The transcription factor SOX9 is essential for multiple steps during skeletal development, including mesenchymal cell chondrogenesis and endochondral bone formation. We recently reported that the human SOX9 proximal promoter region is regulated by the CCAAT-binding factor through two CCAAT boxes located within 100 bp of the transcriptional start site. Here we report that the human SOX9 proximal promoter is also regulated by the cyclic-AMP response element binding protein (CREB) and Sp1. We show by DNaseI protection and EMSA analysis that CREB and Sp1 interact with specific sites within the SOX9 proximal promoter region. By transient transfection analysis we also demonstrate that mutations of the CREB and Sp1 binding sites result in a profound reduction of SOX9 promoter activity. Chromatin immunoprecipitation (ChIP) assay demonstrated that both Sp1 and CREB interact with the SOX9 promoter in vivo. Finally, we demonstrate that IL-1β treatment of chondrocytes isolated from human normal and osteoarthritic (OA) cartilage down-regulates SOX9 promoter activity, an effect accompanied by a reduction of Sp1 binding to the SOX9 proximal promoter.

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“…1B). However, the CAD can activate transcription on its own (3,29,50), which suggests that the CAD is able to reach the end point of polymerase recruitment through its recruitment of TFIID. Neither of these hypotheses has been directly tested by measuring recruitment of RNA polymerase II to a template.…”

mentioning

confidence: 99%

“…Extracellular stimuli that activate protein kinases can lead to phosphorylation of CREB on Ser-133, e.g., by cAMP-activated protein kinase A (PKA), resulting in a further enhancement of transcriptional activation (3,16,50). Mutation of the Ser-133 PKA phosphorylation site in CREB to an alanine abolishes kinase-inducible activation (17,50) but not constitutive activation (3,29,50). We and others have shown that these constitutive and kinase-inducible activities map to two separate and independently acting transcription activation domains: a constitutive activation domain (CAD) responsible for activating constitutive transcription and a kinase-inducible domain (KID) that mediates activation in response to cAMP-activated PKA (3,29,50) and several other kinases (11,15,26,63,68).…”

mentioning

confidence: 99%

“…The CRE-binding protein, CREB, a member of the basic leucine zipper family of transcription factors, binds constitutively to the CRE in the promoter of the target gene (51) and can activate constitutive transcription in the absence of hormonal stimuli (3,29,50). Extracellular stimuli that activate protein kinases can lead to phosphorylation of CREB on Ser-133, e.g., by cAMP-activated protein kinase A (PKA), resulting in a further enhancement of transcriptional activation (3,16,50).…”

mentioning

confidence: 99%

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Recruitment of an RNA Polymerase II Complex Is Mediated by the Constitutive Activation Domain in CREB, Independently of CREB Phosphorylation

Felinski

Kim

Lü

et al. 2001

Molecular and Cellular Biology

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The cAMP response element binding protein (CREB) is a bifunctional transcription activator, exerting its effects through a constitutive activation domain (CAD) and a distinct kinase inducible domain (KID), which requires phosphorylation of Ser-133 for activity. Both CAD and phospho-KID have been proposed to recruit polymerase complexes, but this has not been directly tested. Here, we show that the entire CREB activation domain or the CAD enhanced recruitment of a complex containing TFIID, TFIIB, and RNA polymerase II to a linked promoter. The nuclear extracts used mediated protein kinase A (PKA)-inducible transcription, but phosphorylation of CRG (both of the CREB activation domains fused to the Gal4 DNA binding domain) or KID-G4 did not mediate recruitment of a complex, and mutation of the PKA site in CRG abolished transcription induction by PKA but had no effect upon recruitment. The CREB-binding protein (CBP) was not detected in the recruited complex. Our results support a model for transcription activation in which the interaction between the CREB CAD and hTAFII130 of TFIID promotes the recruitment of a polymerase complex to the promoter.The cAMP response element (CRE) mediates both constitutive and cAMP-induced transcription activation of many genes in a variety of cell types (8,30,40,43,50,52). The CRE-binding protein, CREB, a member of the basic leucine zipper family of transcription factors, binds constitutively to the CRE in the promoter of the target gene (51) and can activate constitutive transcription in the absence of hormonal stimuli (3,29,50). Extracellular stimuli that activate protein kinases can lead to phosphorylation of CREB on Ser-133, e.g., by cAMP-activated protein kinase A (PKA), resulting in a further enhancement of transcriptional activation (3,16,50). Mutation of the Ser-133 PKA phosphorylation site in CREB to an alanine abolishes kinase-inducible activation (17, 50) but not constitutive activation (3, 29, 50). We and others have shown that these constitutive and kinase-inducible activities map to two separate and independently acting transcription activation domains: a constitutive activation domain (CAD) responsible for activating constitutive transcription and a kinase-inducible domain (KID) that mediates activation in response to cAMP-activated PKA (3, 29, 50) and several other kinases (11,15,26,63,68). However, the exact mechanism of action of these domains in stimulating constitutive and kinaseinducible transcription has not been defined.Transcription of a class II gene by RNA polymerase II requires the assembly of general transcription factors and coactivators around the transcription start site in the gene's promoter (reviewed in references 22 and 44). The general transcription factors (TFIID, TFIIA, TFIIB, TFIIF-pol II, TFIIE, and TFIIH) were initially identified as the basic nuclear components required to reconstitute in vitro transcription by RNA polymerase II (9, 54-56, 66, 67). These general factors are required for accurate and optimal positioning of RNA polymerase II at ...

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Distinct cAMP response element-binding protein (CREB) domains stimulate different steps in a concerted mechanism of transcription activation

Cited by 23 publications

References 46 publications

Mechanism of Rapid Transcriptional Induction of Tumor Necrosis Factor Alpha-Responsive Genes by NF-κB

Mechanism of Rapid Transcriptional Induction of Tumor Necrosis Factor Alpha-Responsive Genes by NF-κB

Regulation of the human SOX9 promoter by Sp1 and CREB

Recruitment of an RNA Polymerase II Complex Is Mediated by the Constitutive Activation Domain in CREB, Independently of CREB Phosphorylation

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