Source 1primary paper2016Scientific Reports
Toolkit/optoRAF
optoRAF
Taxonomy: Mechanism Branch / Architecture. Workflows sit above the mechanism and technique branches rather than replacing them.
Summary
optoRAF is an optogenetic multi-component switch for light-controlled clustering and activation of RAF proteins. It was described as mimicking naturally occurring RAS-mediated RAF dimerization and was used to probe BRAF and CRAF responses to kinase inhibitors.
Usefulness & Problems
Why this is useful
This tool is useful for experimentally controlling RAF dimerization-like activation with light while assessing how RAF signaling responds to small-molecule inhibitors. The cited study used it to characterize paradoxical and dose-dependent effects of vemurafenib and dabrafenib on BRAF and CRAF dimers.
Source:
This versatile tool allows studying the effect on BRAF and CRAF homodimer- as well as heterodimer-induced RAF signaling.
Source:
optoRAF, an optogenetic tool for light-controlled clustering and activation of RAF proteins that mimics the natural occurring RAS-mediated dimerization
Problem solved
optoRAF addresses the problem of interrogating RAF activation and inhibitor response in a controllable, optogenetic context that mimics RAS-mediated dimerization. It enables separation of light-driven RAF clustering/activation from drug-dependent modulation of BRAF and CRAF signaling.
Taxonomy & Function
Primary hierarchy
Mechanism Branch
Architecture: A composed arrangement of multiple parts that instantiates one or more mechanisms.
Techniques
No technique tags yet.
Target processes
recombinationsignalingInput: Light
Implementation Constraints
The available evidence supports that optoRAF is an optogenetic, multi-component system based on light-controlled clustering of RAF proteins, but the specific photoreceptor modules, wavelengths, cofactors, and construct designs are not given here. Its demonstrated application was the analysis of BRAF and CRAF signaling under kinase inhibitor treatment, including dabrafenib and vemurafenib.
The supplied evidence is limited to a single 2016 study and does not provide detailed quantitative performance metrics, dynamic range, kinetics, or validation across multiple cell types or organisms. Practical details of the optical system, construct architecture, and any off-target or basal activity are not described in the provided evidence.
Validation
Cell-freeBacteriaMammalianMouseHumanTherapeuticIndep. Replication
Supporting Sources
Ranked Claims
Increased CRAF levels correlate with elevated RAF signaling in a dabrafenib-dependent manner independent of light activation.
Increased CRAF levels correlate with elevated RAF signaling in a dabrafenib-dependent manner, independent of light activation.
Increased CRAF levels correlate with elevated RAF signaling in a dabrafenib-dependent manner independent of light activation.
Increased CRAF levels correlate with elevated RAF signaling in a dabrafenib-dependent manner, independent of light activation.
Increased CRAF levels correlate with elevated RAF signaling in a dabrafenib-dependent manner independent of light activation.
Increased CRAF levels correlate with elevated RAF signaling in a dabrafenib-dependent manner, independent of light activation.
Increased CRAF levels correlate with elevated RAF signaling in a dabrafenib-dependent manner independent of light activation.
Increased CRAF levels correlate with elevated RAF signaling in a dabrafenib-dependent manner, independent of light activation.
Increased CRAF levels correlate with elevated RAF signaling in a dabrafenib-dependent manner independent of light activation.
Increased CRAF levels correlate with elevated RAF signaling in a dabrafenib-dependent manner, independent of light activation.
Increased CRAF levels correlate with elevated RAF signaling in a dabrafenib-dependent manner independent of light activation.
Increased CRAF levels correlate with elevated RAF signaling in a dabrafenib-dependent manner, independent of light activation.
Increased CRAF levels correlate with elevated RAF signaling in a dabrafenib-dependent manner independent of light activation.
Increased CRAF levels correlate with elevated RAF signaling in a dabrafenib-dependent manner, independent of light activation.
Dabrafenib enhanced activity of light-stimulated CRAF at low dose and inhibited CRAF signaling at high dose.
Dabrafenib enhanced activity of light-stimulated CRAF at low dose and inhibited CRAF signaling at high dose.
Dabrafenib enhanced activity of light-stimulated CRAF at low dose and inhibited CRAF signaling at high dose.
Dabrafenib enhanced activity of light-stimulated CRAF at low dose and inhibited CRAF signaling at high dose.
Dabrafenib enhanced activity of light-stimulated CRAF at low dose and inhibited CRAF signaling at high dose.
Dabrafenib enhanced activity of light-stimulated CRAF at low dose and inhibited CRAF signaling at high dose.
Dabrafenib enhanced activity of light-stimulated CRAF at low dose and inhibited CRAF signaling at high dose.
Dabrafenib enhanced activity of light-stimulated CRAF at low dose and inhibited CRAF signaling at high dose.
Dabrafenib enhanced activity of light-stimulated CRAF at low dose and inhibited CRAF signaling at high dose.
Dabrafenib enhanced activity of light-stimulated CRAF at low dose and inhibited CRAF signaling at high dose.
Dabrafenib enhanced activity of light-stimulated CRAF at low dose and inhibited CRAF signaling at high dose.
Dabrafenib enhanced activity of light-stimulated CRAF at low dose and inhibited CRAF signaling at high dose.
Dabrafenib enhanced activity of light-stimulated CRAF at low dose and inhibited CRAF signaling at high dose.
Dabrafenib enhanced activity of light-stimulated CRAF at low dose and inhibited CRAF signaling at high dose.
Using optoRAF, vemurafenib was identified as a paradoxical activator of BRAF and CRAF homo- and heterodimers.
Using optoRAF, vemurafenib was identified as paradoxical activator of BRAF and CRAF homo- and heterodimers.
Using optoRAF, vemurafenib was identified as a paradoxical activator of BRAF and CRAF homo- and heterodimers.
Using optoRAF, vemurafenib was identified as paradoxical activator of BRAF and CRAF homo- and heterodimers.
Using optoRAF, vemurafenib was identified as a paradoxical activator of BRAF and CRAF homo- and heterodimers.
Using optoRAF, vemurafenib was identified as paradoxical activator of BRAF and CRAF homo- and heterodimers.
Using optoRAF, vemurafenib was identified as a paradoxical activator of BRAF and CRAF homo- and heterodimers.
Using optoRAF, vemurafenib was identified as paradoxical activator of BRAF and CRAF homo- and heterodimers.
Using optoRAF, vemurafenib was identified as a paradoxical activator of BRAF and CRAF homo- and heterodimers.
Using optoRAF, vemurafenib was identified as paradoxical activator of BRAF and CRAF homo- and heterodimers.
Using optoRAF, vemurafenib was identified as a paradoxical activator of BRAF and CRAF homo- and heterodimers.
Using optoRAF, vemurafenib was identified as paradoxical activator of BRAF and CRAF homo- and heterodimers.
Using optoRAF, vemurafenib was identified as a paradoxical activator of BRAF and CRAF homo- and heterodimers.
Using optoRAF, vemurafenib was identified as paradoxical activator of BRAF and CRAF homo- and heterodimers.
Dabrafenib increased the protein level of CRAF proteins but not of BRAF proteins.
Moreover, dabrafenib increased the protein level of CRAF proteins but not of BRAF proteins.
Dabrafenib increased the protein level of CRAF proteins but not of BRAF proteins.
Moreover, dabrafenib increased the protein level of CRAF proteins but not of BRAF proteins.
Dabrafenib increased the protein level of CRAF proteins but not of BRAF proteins.
Moreover, dabrafenib increased the protein level of CRAF proteins but not of BRAF proteins.
Dabrafenib increased the protein level of CRAF proteins but not of BRAF proteins.
Moreover, dabrafenib increased the protein level of CRAF proteins but not of BRAF proteins.
Dabrafenib increased the protein level of CRAF proteins but not of BRAF proteins.
Moreover, dabrafenib increased the protein level of CRAF proteins but not of BRAF proteins.
Dabrafenib increased the protein level of CRAF proteins but not of BRAF proteins.
Moreover, dabrafenib increased the protein level of CRAF proteins but not of BRAF proteins.
Dabrafenib increased the protein level of CRAF proteins but not of BRAF proteins.
Moreover, dabrafenib increased the protein level of CRAF proteins but not of BRAF proteins.
optoRAF allows study of BRAF and CRAF homodimer- and heterodimer-induced RAF signaling.
This versatile tool allows studying the effect on BRAF and CRAF homodimer- as well as heterodimer-induced RAF signaling.
optoRAF allows study of BRAF and CRAF homodimer- and heterodimer-induced RAF signaling.
This versatile tool allows studying the effect on BRAF and CRAF homodimer- as well as heterodimer-induced RAF signaling.
optoRAF allows study of BRAF and CRAF homodimer- and heterodimer-induced RAF signaling.
This versatile tool allows studying the effect on BRAF and CRAF homodimer- as well as heterodimer-induced RAF signaling.
optoRAF allows study of BRAF and CRAF homodimer- and heterodimer-induced RAF signaling.
This versatile tool allows studying the effect on BRAF and CRAF homodimer- as well as heterodimer-induced RAF signaling.
optoRAF allows study of BRAF and CRAF homodimer- and heterodimer-induced RAF signaling.
This versatile tool allows studying the effect on BRAF and CRAF homodimer- as well as heterodimer-induced RAF signaling.
optoRAF allows study of BRAF and CRAF homodimer- and heterodimer-induced RAF signaling.
This versatile tool allows studying the effect on BRAF and CRAF homodimer- as well as heterodimer-induced RAF signaling.
optoRAF allows study of BRAF and CRAF homodimer- and heterodimer-induced RAF signaling.
This versatile tool allows studying the effect on BRAF and CRAF homodimer- as well as heterodimer-induced RAF signaling.
optoRAF is an optogenetic tool for light-controlled clustering and activation of RAF proteins that mimics naturally occurring RAS-mediated dimerization.
optoRAF, an optogenetic tool for light-controlled clustering and activation of RAF proteins that mimics the natural occurring RAS-mediated dimerization
optoRAF is an optogenetic tool for light-controlled clustering and activation of RAF proteins that mimics naturally occurring RAS-mediated dimerization.
optoRAF, an optogenetic tool for light-controlled clustering and activation of RAF proteins that mimics the natural occurring RAS-mediated dimerization
optoRAF is an optogenetic tool for light-controlled clustering and activation of RAF proteins that mimics naturally occurring RAS-mediated dimerization.
optoRAF, an optogenetic tool for light-controlled clustering and activation of RAF proteins that mimics the natural occurring RAS-mediated dimerization
optoRAF is an optogenetic tool for light-controlled clustering and activation of RAF proteins that mimics naturally occurring RAS-mediated dimerization.
optoRAF, an optogenetic tool for light-controlled clustering and activation of RAF proteins that mimics the natural occurring RAS-mediated dimerization
optoRAF is an optogenetic tool for light-controlled clustering and activation of RAF proteins that mimics naturally occurring RAS-mediated dimerization.
optoRAF, an optogenetic tool for light-controlled clustering and activation of RAF proteins that mimics the natural occurring RAS-mediated dimerization
optoRAF is an optogenetic tool for light-controlled clustering and activation of RAF proteins that mimics naturally occurring RAS-mediated dimerization.
optoRAF, an optogenetic tool for light-controlled clustering and activation of RAF proteins that mimics the natural occurring RAS-mediated dimerization
optoRAF is an optogenetic tool for light-controlled clustering and activation of RAF proteins that mimics naturally occurring RAS-mediated dimerization.
optoRAF, an optogenetic tool for light-controlled clustering and activation of RAF proteins that mimics the natural occurring RAS-mediated dimerization
Approval Evidence
1 source6 linked approval claimsfirst-pass slug optoraf
optoRAF, an optogenetic tool for light-controlled clustering and activation of RAF proteins that mimics the natural occurring RAS-mediated dimerization
Source:
correlationsupports
Increased CRAF levels correlate with elevated RAF signaling in a dabrafenib-dependent manner independent of light activation.
Increased CRAF levels correlate with elevated RAF signaling in a dabrafenib-dependent manner, independent of light activation.
Source:
dose dependent drug effectsupports
Dabrafenib enhanced activity of light-stimulated CRAF at low dose and inhibited CRAF signaling at high dose.
Dabrafenib enhanced activity of light-stimulated CRAF at low dose and inhibited CRAF signaling at high dose.
Source:
drug effectsupports
Using optoRAF, vemurafenib was identified as a paradoxical activator of BRAF and CRAF homo- and heterodimers.
Using optoRAF, vemurafenib was identified as paradoxical activator of BRAF and CRAF homo- and heterodimers.
Source:
protein level effectsupports
Dabrafenib increased the protein level of CRAF proteins but not of BRAF proteins.
Moreover, dabrafenib increased the protein level of CRAF proteins but not of BRAF proteins.
Source:
tool capabilitysupports
optoRAF allows study of BRAF and CRAF homodimer- and heterodimer-induced RAF signaling.
This versatile tool allows studying the effect on BRAF and CRAF homodimer- as well as heterodimer-induced RAF signaling.
Source:
tool functionsupports
optoRAF is an optogenetic tool for light-controlled clustering and activation of RAF proteins that mimics naturally occurring RAS-mediated dimerization.
optoRAF, an optogenetic tool for light-controlled clustering and activation of RAF proteins that mimics the natural occurring RAS-mediated dimerization
Source:
Comparisons
Source-backed strengths
The reported strength of optoRAF is its ability to impose light-controlled RAF clustering and activation in a manner intended to mimic native RAS-mediated dimerization. In the cited work, it revealed that vemurafenib acts as a paradoxical activator of BRAF and CRAF homo- and heterodimers, and that dabrafenib enhanced light-stimulated CRAF at low dose but inhibited CRAF signaling at high dose.
Ranked Citations
- 1.