Source 1primary paper2012Proceedings of the National Academy of Sciences
Toolkit/synthetic promoters containing CREB1-specific cAMP response elements
synthetic promoters containing CREB1-specific cAMP response elements
Taxonomy: Mechanism Branch / Architecture. Workflows sit above the mechanism and technique branches rather than replacing them.
Summary
Synthetic promoters containing CREB1-specific cAMP response elements are engineered transcriptional control sequences used in a designer signaling circuit. In the cited system, they convert cTAAR1-driven cAMP/PKA activation of CREB1 into inducible transgene expression.
Usefulness & Problems
Why this is useful
These promoters are useful for coupling an upstream pharmacologically triggered signaling pathway to transcriptional output. In the reported designer circuit, they enabled guanabenz-responsive control of therapeutic gene expression downstream of rewired cTAAR1 signaling.
Source:
In mice developing symptoms of the metabolic syndrome, this three-in-one treatment strategy was able to simultaneously attenuate hypertension and hyperglycemia as well as obesity and dyslipidemia
Problem solved
They address the problem of translating cTAAR1-mediated intracellular cAMP/PKA signaling into programmable gene expression. Specifically, they provide a synthetic transcriptional interface that links CREB1 activation to expression of payload genes such as GLP-1-Fc(mIgG)-Leptin.
Source:
In mice developing symptoms of the metabolic syndrome, this three-in-one treatment strategy was able to simultaneously attenuate hypertension and hyperglycemia as well as obesity and dyslipidemia
Problem links
Need conditional control of signaling activity
DerivedSynthetic promoters containing CREB1-specific cAMP response elements are engineered transcriptional control sequences used in a designer signaling circuit. In the cited system, they convert cTAAR1-driven cAMP/PKA activation of CREB1 into inducible transgene expression.
Need conditional recombination or state switching
DerivedSynthetic promoters containing CREB1-specific cAMP response elements are engineered transcriptional control sequences used in a designer signaling circuit. In the cited system, they convert cTAAR1-driven cAMP/PKA activation of CREB1 into inducible transgene expression.
Need tighter control over gene expression timing or amplitude
DerivedSynthetic promoters containing CREB1-specific cAMP response elements are engineered transcriptional control sequences used in a designer signaling circuit. In the cited system, they convert cTAAR1-driven cAMP/PKA activation of CREB1 into inducible transgene expression.
Taxonomy & Function
Primary hierarchy
Mechanism Branch
Architecture: A reusable architecture pattern for arranging parts into an engineered system.
Techniques
No technique tags yet.
Target processes
recombinationsignalingtranscriptionImplementation Constraints
cofactor dependency: cofactor requirement unknownencoding mode: genetically encodedimplementation constraint: context specific validationoperating role: regulator
The reported implementation places these synthetic promoters downstream of a rewired cTAAR1 signaling module that activates CREB1 via cAMP/PKA. Practical construct details beyond the presence of CREB1-specific cAMP response elements are not provided in the supplied evidence.
Evidence is limited to a single cited study and a specific circuit context involving cTAAR1, CREB1, and therapeutic transgene expression. The supplied evidence does not report promoter sequence architecture, dynamic range, basal leak, cell-type generality, or independent replication.
Validation
Cell-freeBacteriaMammalianMouseHumanTherapeuticIndep. Replication
Supporting Sources
Ranked Claims
Guanabenz activates a synthetic signal cascade that stimulates secretion of GLP-1 and leptin.
the clinically licensed antihypertensive drug guanabenz (Wytensin) activates a synthetic signal cascade that stimulates the secretion of metabolically active peptides GLP-1 and leptin
Guanabenz activates a synthetic signal cascade that stimulates secretion of GLP-1 and leptin.
the clinically licensed antihypertensive drug guanabenz (Wytensin) activates a synthetic signal cascade that stimulates the secretion of metabolically active peptides GLP-1 and leptin
Guanabenz activates a synthetic signal cascade that stimulates secretion of GLP-1 and leptin.
the clinically licensed antihypertensive drug guanabenz (Wytensin) activates a synthetic signal cascade that stimulates the secretion of metabolically active peptides GLP-1 and leptin
Guanabenz activates a synthetic signal cascade that stimulates secretion of GLP-1 and leptin.
the clinically licensed antihypertensive drug guanabenz (Wytensin) activates a synthetic signal cascade that stimulates the secretion of metabolically active peptides GLP-1 and leptin
Guanabenz activates a synthetic signal cascade that stimulates secretion of GLP-1 and leptin.
the clinically licensed antihypertensive drug guanabenz (Wytensin) activates a synthetic signal cascade that stimulates the secretion of metabolically active peptides GLP-1 and leptin
Guanabenz activates a synthetic signal cascade that stimulates secretion of GLP-1 and leptin.
the clinically licensed antihypertensive drug guanabenz (Wytensin) activates a synthetic signal cascade that stimulates the secretion of metabolically active peptides GLP-1 and leptin
Guanabenz activates a synthetic signal cascade that stimulates secretion of GLP-1 and leptin.
the clinically licensed antihypertensive drug guanabenz (Wytensin) activates a synthetic signal cascade that stimulates the secretion of metabolically active peptides GLP-1 and leptin
Guanabenz dose-dependently controls expression of GLP-1-Fc(mIgG)-Leptin.
it was possible to use guanabenz to dose-dependently control expression of GLP-1-Fc(mIgG)-Leptin
Guanabenz dose-dependently controls expression of GLP-1-Fc(mIgG)-Leptin.
it was possible to use guanabenz to dose-dependently control expression of GLP-1-Fc(mIgG)-Leptin
Guanabenz dose-dependently controls expression of GLP-1-Fc(mIgG)-Leptin.
it was possible to use guanabenz to dose-dependently control expression of GLP-1-Fc(mIgG)-Leptin
Guanabenz dose-dependently controls expression of GLP-1-Fc(mIgG)-Leptin.
it was possible to use guanabenz to dose-dependently control expression of GLP-1-Fc(mIgG)-Leptin
Guanabenz dose-dependently controls expression of GLP-1-Fc(mIgG)-Leptin.
it was possible to use guanabenz to dose-dependently control expression of GLP-1-Fc(mIgG)-Leptin
Guanabenz dose-dependently controls expression of GLP-1-Fc(mIgG)-Leptin.
it was possible to use guanabenz to dose-dependently control expression of GLP-1-Fc(mIgG)-Leptin
Guanabenz dose-dependently controls expression of GLP-1-Fc(mIgG)-Leptin.
it was possible to use guanabenz to dose-dependently control expression of GLP-1-Fc(mIgG)-Leptin
Signal transduction of cTAAR1 was functionally rewired through cAMP/PKA-mediated activation of CREB1 to drive transcription from synthetic promoters containing CREB1-specific cAMP response elements.
the signal transduction of a chimeric trace-amine-associated receptor 1 (cTAAR1) was functionally rewired via cAMP and cAMP-dependent phosphokinase A (PKA)-mediated activation of the cAMP-response element binding protein (CREB1) to transcription of synthetic promoters containing CREB1-specific cAMP response elements
Signal transduction of cTAAR1 was functionally rewired through cAMP/PKA-mediated activation of CREB1 to drive transcription from synthetic promoters containing CREB1-specific cAMP response elements.
the signal transduction of a chimeric trace-amine-associated receptor 1 (cTAAR1) was functionally rewired via cAMP and cAMP-dependent phosphokinase A (PKA)-mediated activation of the cAMP-response element binding protein (CREB1) to transcription of synthetic promoters containing CREB1-specific cAMP response elements
Signal transduction of cTAAR1 was functionally rewired through cAMP/PKA-mediated activation of CREB1 to drive transcription from synthetic promoters containing CREB1-specific cAMP response elements.
the signal transduction of a chimeric trace-amine-associated receptor 1 (cTAAR1) was functionally rewired via cAMP and cAMP-dependent phosphokinase A (PKA)-mediated activation of the cAMP-response element binding protein (CREB1) to transcription of synthetic promoters containing CREB1-specific cAMP response elements
Signal transduction of cTAAR1 was functionally rewired through cAMP/PKA-mediated activation of CREB1 to drive transcription from synthetic promoters containing CREB1-specific cAMP response elements.
the signal transduction of a chimeric trace-amine-associated receptor 1 (cTAAR1) was functionally rewired via cAMP and cAMP-dependent phosphokinase A (PKA)-mediated activation of the cAMP-response element binding protein (CREB1) to transcription of synthetic promoters containing CREB1-specific cAMP response elements
Signal transduction of cTAAR1 was functionally rewired through cAMP/PKA-mediated activation of CREB1 to drive transcription from synthetic promoters containing CREB1-specific cAMP response elements.
the signal transduction of a chimeric trace-amine-associated receptor 1 (cTAAR1) was functionally rewired via cAMP and cAMP-dependent phosphokinase A (PKA)-mediated activation of the cAMP-response element binding protein (CREB1) to transcription of synthetic promoters containing CREB1-specific cAMP response elements
Signal transduction of cTAAR1 was functionally rewired through cAMP/PKA-mediated activation of CREB1 to drive transcription from synthetic promoters containing CREB1-specific cAMP response elements.
the signal transduction of a chimeric trace-amine-associated receptor 1 (cTAAR1) was functionally rewired via cAMP and cAMP-dependent phosphokinase A (PKA)-mediated activation of the cAMP-response element binding protein (CREB1) to transcription of synthetic promoters containing CREB1-specific cAMP response elements
Signal transduction of cTAAR1 was functionally rewired through cAMP/PKA-mediated activation of CREB1 to drive transcription from synthetic promoters containing CREB1-specific cAMP response elements.
the signal transduction of a chimeric trace-amine-associated receptor 1 (cTAAR1) was functionally rewired via cAMP and cAMP-dependent phosphokinase A (PKA)-mediated activation of the cAMP-response element binding protein (CREB1) to transcription of synthetic promoters containing CREB1-specific cAMP response elements
In mice developing symptoms of metabolic syndrome, the three-in-one treatment strategy simultaneously attenuated hypertension, hyperglycemia, obesity, and dyslipidemia.
In mice developing symptoms of the metabolic syndrome, this three-in-one treatment strategy was able to simultaneously attenuate hypertension and hyperglycemia as well as obesity and dyslipidemia
In mice developing symptoms of metabolic syndrome, the three-in-one treatment strategy simultaneously attenuated hypertension, hyperglycemia, obesity, and dyslipidemia.
In mice developing symptoms of the metabolic syndrome, this three-in-one treatment strategy was able to simultaneously attenuate hypertension and hyperglycemia as well as obesity and dyslipidemia
In mice developing symptoms of metabolic syndrome, the three-in-one treatment strategy simultaneously attenuated hypertension, hyperglycemia, obesity, and dyslipidemia.
In mice developing symptoms of the metabolic syndrome, this three-in-one treatment strategy was able to simultaneously attenuate hypertension and hyperglycemia as well as obesity and dyslipidemia
In mice developing symptoms of metabolic syndrome, the three-in-one treatment strategy simultaneously attenuated hypertension, hyperglycemia, obesity, and dyslipidemia.
In mice developing symptoms of the metabolic syndrome, this three-in-one treatment strategy was able to simultaneously attenuate hypertension and hyperglycemia as well as obesity and dyslipidemia
In mice developing symptoms of metabolic syndrome, the three-in-one treatment strategy simultaneously attenuated hypertension, hyperglycemia, obesity, and dyslipidemia.
In mice developing symptoms of the metabolic syndrome, this three-in-one treatment strategy was able to simultaneously attenuate hypertension and hyperglycemia as well as obesity and dyslipidemia
In mice developing symptoms of metabolic syndrome, the three-in-one treatment strategy simultaneously attenuated hypertension, hyperglycemia, obesity, and dyslipidemia.
In mice developing symptoms of the metabolic syndrome, this three-in-one treatment strategy was able to simultaneously attenuate hypertension and hyperglycemia as well as obesity and dyslipidemia
In mice developing symptoms of metabolic syndrome, the three-in-one treatment strategy simultaneously attenuated hypertension, hyperglycemia, obesity, and dyslipidemia.
In mice developing symptoms of the metabolic syndrome, this three-in-one treatment strategy was able to simultaneously attenuate hypertension and hyperglycemia as well as obesity and dyslipidemia
Approval Evidence
1 source1 linked approval claimfirst-pass slug synthetic-promoters-containing-creb1-specific-camp-response-elements
transcription of synthetic promoters containing CREB1-specific cAMP response elements
Source:
mechanistic designsupports
Signal transduction of cTAAR1 was functionally rewired through cAMP/PKA-mediated activation of CREB1 to drive transcription from synthetic promoters containing CREB1-specific cAMP response elements.
the signal transduction of a chimeric trace-amine-associated receptor 1 (cTAAR1) was functionally rewired via cAMP and cAMP-dependent phosphokinase A (PKA)-mediated activation of the cAMP-response element binding protein (CREB1) to transcription of synthetic promoters containing CREB1-specific cAMP response elements
Source:
Comparisons
Source-backed strengths
The source reports that guanabenz dose-dependently controlled expression of GLP-1-Fc(mIgG)-Leptin through this circuit architecture. The promoters therefore supported signal-dependent transcriptional activation in a pharmacologically actuated designer system.
Compared with CAR-NK
synthetic promoters containing CREB1-specific cAMP response elements and CAR-NK address a similar problem space because they share recombination, signaling.
Shared frame: same top-level item type; shared target processes: recombination, signaling
Relative tradeoffs: appears more independently replicated; looks easier to implement in practice.
Compared with chimeric trace-amine-associated receptor 1
synthetic promoters containing CREB1-specific cAMP response elements and chimeric trace-amine-associated receptor 1 address a similar problem space because they share recombination, signaling, transcription.
Shared frame: same top-level item type; shared target processes: recombination, signaling, transcription; shared mechanisms: camp/pka-mediated creb1 activation
Compared with synthetic promoters
synthetic promoters containing CREB1-specific cAMP response elements and synthetic promoters address a similar problem space because they share recombination, transcription.
Shared frame: same top-level item type; shared target processes: recombination, transcription
Relative tradeoffs: appears more independently replicated; looks easier to implement in practice.
Ranked Citations
- 1.