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.

The transcriptional activity of Pygopus is enhanced by its interaction with cAMP-response-element-binding protein (CREB)-binding protein

2009 ◽  
Vol 422 (3) ◽  
pp. 493-501 ◽  
Author(s):  
Phillip G. P. Andrews ◽  
Zhijian He ◽  
Cathy Popadiuk ◽  
Kenneth R. Kao
Keyword(s):  
Histone Acetylation ◽  
Transcriptional Activation ◽  
Transcriptional Activity ◽  
Target Genes ◽  
Histone Acetyltransferase ◽  
Binding Protein ◽  
Camp Response Element Binding ◽  
Creb Binding Protein ◽  
Hek 293 ◽  
Element Binding Protein

Pygopus is a core component of the β-catenin/TCF (T-cell factor) transcriptional activation complex required for the expression of canonical Wnt target genes. Recent evidence suggests that Pygopus could interpret histone methylation associated with target genes and it was shown to be required for histone acetylation. The involvement of a specific acetyltransferase, however, was not determined. In this report, we demonstrate that Pygopus can interact with the HAT (histone acetyltransferase) CBP [CREB (cAMP-responsive-element-binding protein)-binding protein]. The interaction is via the NHD (N-terminal homology domain) of Pygopus, which binds to two regions in the vicinity of the HAT domain of CBP. Transfected and endogenous hPygo2 (human Pygopus2) and CBP proteins co-immunoprecipitate in HEK-293 (human embryonic kidney 293) cells and both proteins co-localize in SW480 colorectal cancer cells. The interaction with CBP also enhances both DNA-tethered and TCF/LEF1 (lymphoid enhancing factor 1)-dependent transcriptional activity of Pygopus. Furthermore, immunoprecipitated Pygopus protein complexes displayed CBP-dependent histone acetyltransferase activity. Our data support a model in which the NHD region of Pygopus is required to augment TCF/β-catenin-mediated transcriptional activation by a mechanism that includes both transcriptional activation and histone acetylation resulting from the recruitment of the CBP histone acetyltransferase.

scholarly journals Mitochondrial Cyclic AMP Response Element-binding Protein (CREB) Mediates Mitochondrial Gene Expression and Neuronal Survival

2005 ◽  
Vol 280 (49) ◽  
pp. 40398-40401 ◽  
Author(s):  
Junghee Lee ◽  
Chun-Hyung Kim ◽  
David K. Simon ◽  
Lyaylya R. Aminova ◽  
Alexander Y. Andreyev ◽  
...  
Keyword(s):  
Gene Expression ◽  
Cyclic Amp ◽  
Neuronal Survival ◽  
Binding Protein ◽  
Mitochondrial Gene ◽  
Mitochondrial Gene Expression ◽  
Response Element ◽  
Element Binding Protein ◽  
Cyclic Amp Response Element

UV stimulation induces nuclear factor κB (NF-κB) DNA-binding activity but not transcriptional activation

2001 ◽  
Vol 29 (6) ◽  
pp. 688-691 ◽  
Author(s):  
K. J. Campbell ◽  
N. R. Chapman ◽  
N. D. Perkins
Keyword(s):  
Dna Binding ◽  
Transcriptional Activation ◽  
Cellular Response ◽  
Uv Light ◽  
Binding Protein ◽  
Nuclear Factor Κb ◽  
Camp Response Element Binding ◽  
Binding Activity ◽  
Nuclear Factor ◽  
Dna Binding Activity

The cellular response to DNA-damaging agents is partly mediated by DNA-binding transcription factors such as p53 and nuclear factor κB (NF-κB). Typically NF-κB activation is associated with resistance to apoptosis. Following stimulation with UV light however, NF-κB activation has been shown to be required for programmed cell death. To study this effect further and to determine the relationship between NF-κB and p53 function, we have examined the effect of UV light on U2OS cells. UV stimulation resulted in the activation of NF-κB DNA-binding and the induction of p53. Surprisingly, and in contrast with tumour necrosis factor α stimulation, this UV-induced NF-κB was transcriptionally inert. These observations suggest a model in which the NF-κB switch from an anti-apoptotic to a pro-apoptotic role within the cell results from modulation of its ability to stimulate gene expression, possibly as a result of the ability of p53 to sequester transcriptional co-activator proteins such as p300/CREB (cAMP-response-element-binding protein)-binding protein.

Nuclear Factor-κB–Dependent Induction of Interleukin-8 Gene Expression by Tumor Necrosis Factor : Evidence for an Antioxidant Sensitive Activating Pathway Distinct From Nuclear Translocation

Blood ◽  
1999 ◽  
Vol 94 (6) ◽  
pp. 1878-1889 ◽  
Author(s):  
Spiros Vlahopoulos ◽  
Istvan Boldogh ◽  
Antonella Casola ◽  
Allan R. Brasier
Keyword(s):  
Gene Expression ◽  
Tumor Necrosis Factor ◽  
Transcriptional Activation ◽  
Tumor Necrosis ◽  
Nuclear Translocation ◽  
Gene Transfection ◽  
Nuclear Factor Κb ◽  
Interleukin 8 ◽  
Nuclear Factor ◽  
Necrosis Factor

Tumor necrosis factor  (TNF) is a pluripotent activator of inflammation by inducing a proinflammatory cytokine cascade. This phenomenon is mediated, in part, through inducible expression of the CXC chemokine, interleukin-8 (IL-8). In this study, we investigate the role of TNF-inducible reactive oxygen species (ROS) in IL-8 expression by “monocyte-like” U937 histiocytic lymphoma cells. TNF is a rapid activator of IL-8 gene expression by U937, producing a 50-fold induction of mRNA within 1 hour of treatment. In gene transfection assays, the effect of TNF requires the presence of an inducible nuclear factor-κB (NF-κB) (Rel A) binding site in the IL-8 promoter. TNF treatment induces a rapid translocation of the 65 kD transcriptional activator NF-κB subunit, Rel A, whose binding in the nucleus occurs before changes in intracellular ROS. Pretreatment (or up to 15 minutes posttreatment) relative to TNF with the antioxidant dimethyl sulfoxide (DMSO) (2% [vol/vol]) blocks 80% of NF-κB–dependent transcription. Surprisingly, however, DMSO has no effect on inducible Rel A binding. Similar selective effects on NF-κB transcription are seen with the unrelated antioxidants, N-acetylcysteine (NAC) and vitamin C. These data indicate that TNF induces a delayed ROS-dependent signalling pathway that is required for NF-κB transcriptional activation and is separable from that required for its nuclear translocation. Further definition of this pathway will yield new insights into inflammation initiated by TNF signalling.

scholarly journals Presenilins Regulate Neurotrypsin Gene Expression and Neurotrypsin-dependent Agrin Cleavage via Cyclic AMP Response Element-binding Protein (CREB) Modulation

2013 ◽  
Vol 288 (49) ◽  
pp. 35222-35236 ◽  
Author(s):  
Angels Almenar-Queralt ◽  
Sonia N. Kim ◽  
Christopher Benner ◽  
Cheryl M. Herrera ◽  
David E. Kang ◽  
...  
Keyword(s):  
Gene Expression ◽  
Cyclic Amp ◽  
Binding Protein ◽  
Response Element ◽  
Element Binding Protein ◽  
Cyclic Amp Response Element
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