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

Cardinaux, Jean‐René; Notis, John C.; Zhang, Qinghong; Vo, Ngan; Craig, Johanna C.; Brennan, Richard G.; Goodman, Richard H.

doi:10.1128/mcb.20.5.1546-1552.2000

Cited by 167 publications

(182 citation statements)

References 40 publications

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“…3). This is consistent with the suggestion that CRE-mediated gene expression are activated if a stable CREB-CBP complex can be formed (63,64).…”

Section: Discussionsupporting

confidence: 79%

Multiple Signals Required for Cyclic AMP-Responsive Element Binding Protein (CREB) Binding Protein Interaction Induced by CD3/CD28 Costimulation

Shih²,

Lai

2001

The Journal of Immunology

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The optimal activation of cAMP-responsive element binding protein (CREB), similar to the full activation of T lymphocytes, requires the stimulation of both CD3 and CD28. Using a reporter system to detect interaction of CREB and CREB-binding protein (CBP), in this study we found that CREB binds to CBP only by engagement of both CD3 and CD28. CD3/CD28-promoted CREB-CBP interaction was dependent on p38 mitogen-activated protein kinase (MAPK) and calcium/calmodulin-dependent protein kinase (CaMK) IV in addition to the previously identified extracellular signal-regulated kinase pathway. Extracellular signal-regulated kinase, CaMKIV, and p38 MAPK were also the kinases involved in CREB Ser133 phosphorylation induced by CD3/CD28. A reconstitution experiment illustrated that optimum CREB-CBP interaction and CREB trans-activation were attained when these three kinase pathways were simultaneously activated in T cells. Our results demonstrate that coordinated activation of different kinases leads to full activation of CREB. Notably, CD28 ligation activated p38 MAPK and CaMKIV, the kinases stimulated by CD3 engagement, suggesting that CD28 acts by increasing the activation extent of p38 MAPK and CaMKIV. These results support the model of a minimum activation threshold for CREB-CBP interaction that can be reached only when both CD3 and CD28 are stimulated.

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“…3). This is consistent with the suggestion that CRE-mediated gene expression are activated if a stable CREB-CBP complex can be formed (63,64).…”

Section: Discussionsupporting

confidence: 79%

Multiple Signals Required for Cyclic AMP-Responsive Element Binding Protein (CREB) Binding Protein Interaction Induced by CD3/CD28 Costimulation

Shih²,

Lai

2001

The Journal of Immunology

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“…Recruitment of the CREB-binding protein, CBP, is sufficient for CREB-mediated gene activation (68). CBP binds to components of the basal transcriptional machinery and may act as a scaffold to stabilize the preinitiation complex at the promoter (69).…”

Section: Figmentioning

confidence: 99%

Persistent TrkA Activity Is Necessary to Maintain Transcription in Neuronally Differentiated PC12 Cells

Chang

Mellon

Schanen

et al. 2003

Journal of Biological Chemistry

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Neurotrophins are required for the differentiation and survival of several different neuronal subpopulations in the developing nervous system. The PC12 cell line responds to nerve growth factor (NGF) by withdrawing from the cell cycle and acquiring a sympathetic neuronlike phenotype. Previous studies have shown that the activation kinetics of the NGF receptor, TrkA, and downstream protein kinases appear rapid and seemingly transient after NGF treatment of naive PC12 cells. However, maintenance of the neuronal phenotype and survival of differentiated PC12 cells under serum-free conditions require constant NGF exposure. In this study we have addressed the mechanisms that NGF uses to maintain neuronal PC12 cells. We show that TrkA remains phosphorylated at a basal level throughout differentiation of the PC12 cells. The phospho-TrkA levels in the differentiated PC12 cells were diminished by both complete NGF withdrawal and pharmacological inhibition of Trk kinase activity. Intracellular sequestration of the majority of TrkA molecules (both phosphorylated and nonphosphorylated TrkA) and persistent dephosphorylation of the small pool of cell surface TrkA renders the persistent phospho-TrkA signal in the differentiated PC12 cells resistant to partial NGF withdrawal as well as exposure to additional NGF. NGF regulated both extracellular-regulated kinases 1/2 and Akt activity in the differentiated PC12 cells via sustained TrkA activity. Moreover, analysis of transcription using activating protein 1-, serum response element-, and cyclic AMP response element-Luc reporter constructs showed that NGF regulated these promoters through TrkA activity in differentiated PC12 cells. Interestingly, the initial response of the cyclic AMP response element promoter to NGF was delayed, becoming Trk-dependent well beyond the peaks in TrkA and downstream protein kinase signal transduction.During development, nerve growth factor (NGF) 1 has profound effects on the differentiation and survival of subsets of neurons in the peripheral and central nervous systems (1). These effects are largely mediated through activation of the TrkA receptor, which initiates a cascade of signaling events that includes activation of several downstream protein kinases and transcription factors (2). These early events are thought to generate the long term changes in gene expression needed for acquisition of a mature neuronal phenotype. Mature or adult neurons are also exposed to and responsive to neurotrophins like NGF, but their biological responses may be quite distinct from those of an immature neuron. For example, developing nociceptive neurons in the dorsal root ganglion require NGF for survival (3). NGF alters neurite outgrowth, gene induction, and the responsiveness of adult nociceptive neurons to some stimuli, but it is apparently not necessary for their survival (4 -6). Much effort has been devoted toward understanding how NGF and other neurotrophins bring about their biological effects in both the developing and adult nervous systems. Most studies of ne...

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“…Ser-133 phosphorylation promotes target gene activation in part by means of recruitment of the coactivator paralogs CREB-binding protein (CBP)͞p300 (4). Recruitment of CBP by phospho-CREB (P-CREB) appears sufficient for induction of cellular genes in response to cAMP (5,6); in vitro transcription studies indicate that P-CREB is capable of promoting assembly of the transcriptional apparatus independent of other regulatory inputs (7).…”

mentioning

confidence: 99%

Genome-wide analysis of cAMP-response element binding protein occupancy, phosphorylation, and target gene activation in human tissues

Zhang

Odom

Koo

et al. 2005

Proc. Natl. Acad. Sci. U.S.A.

902

867

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Hormones and nutrients often induce genetic programs via signaling pathways that interface with gene-specific activators. Activation of the cAMP pathway, for example, stimulates cellular gene expression by means of the PKA-mediated phosphorylation of cAMP-response element binding protein (CREB) at Ser-133. Here, we use genome-wide approaches to characterize target genes that are regulated by CREB in different cellular contexts. CREB was found to occupy Ϸ4,000 promoter sites in vivo, depending on the presence and methylation state of consensus cAMP response elements near the promoter. The profiles for CREB occupancy were very similar in different human tissues, and exposure to a cAMP agonist stimulated CREB phosphorylation over a majority of these sites. Only a small proportion of CREB target genes was induced by cAMP in any cell type, however, due in part to the preferential recruitment of the coactivator CREB-binding protein to those promoters. These results indicate that CREB phosphorylation alone is not a reliable predictor of target gene activation and that additional CREB regulatory partners are required for recruitment of the transcriptional apparatus to the promoter.cAMP ͉ cAMP-response element binding protein-binding protein ͉ DNA methylation T he concept of a transcription code that dictates gene expression by means of the concerted action of multiple promoter elements has served as a useful paradigm for understanding specificity in gene regulation. The ability of multiple transcription factors to recruit RNA polymerase II to the promoter by means of low affinity interactions with components of the transcriptional machinery has been documented extensively (1).By contrast with this model, other studies suggest that some activators per se are sufficient to mediate transcriptional responses to hormonal signals depending on the occupancy of relevant sites (1). Indeed, genome-wide studies comparing binding patterns of hepatic nuclear factors in the liver and endocrine pancreas indicate that selective occupancy may often explain how different genetic programs are activated in distinct cell types (2).The cAMP-response element binding protein (CREB) family of activators stimulates cellular gene expression after phosphorylation at a conserved serine (Ser-133 in CREB1) in response to cAMP (3). Ser-133 phosphorylation promotes target gene activation in part by means of recruitment of the coactivator paralogs CREB-binding protein (CBP)͞p300 (4). Recruitment of CBP by phospho-CREB (P-CREB) appears sufficient for induction of cellular genes in response to cAMP (5, 6); in vitro transcription studies indicate that P-CREB is capable of promoting assembly of the transcriptional apparatus independent of other regulatory inputs (7).By contrast, some reports suggest that other upstream activators in addition to CREB are required for cellular gene induction by cAMP (8). Indeed, the notion that CREB coordinates with other transcription factors is supported by recent animal studies in which CREB appeared to elicit the expressi...

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

Cited by 167 publications

References 40 publications

Multiple Signals Required for Cyclic AMP-Responsive Element Binding Protein (CREB) Binding Protein Interaction Induced by CD3/CD28 Costimulation

Multiple Signals Required for Cyclic AMP-Responsive Element Binding Protein (CREB) Binding Protein Interaction Induced by CD3/CD28 Costimulation

Persistent TrkA Activity Is Necessary to Maintain Transcription in Neuronally Differentiated PC12 Cells

Genome-wide analysis of cAMP-response element binding protein occupancy, phosphorylation, and target gene activation in human tissues

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