Toolkit/optoRAF

optoRAF

Multi-Component Switch·Research·Since 2016

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.

Problem links

Need conditional control of signaling activity

Derived

optoRAF is an optogenetic multi-component switch for light-controlled clustering and activation of RAF proteins. It is described as mimicking naturally occurring RAS-mediated RAF dimerization and was used to interrogate BRAF and CRAF responses to kinase inhibitors.

Need conditional recombination or state switching

Derived

optoRAF is an optogenetic multi-component switch for light-controlled clustering and activation of RAF proteins. It is described as mimicking naturally occurring RAS-mediated RAF dimerization and was used to interrogate BRAF and CRAF responses to kinase inhibitors.

Need precise spatiotemporal control with light input

Derived

optoRAF is an optogenetic multi-component switch for light-controlled clustering and activation of RAF proteins. It is described as mimicking naturally occurring RAS-mediated RAF dimerization and was used to interrogate BRAF and CRAF responses to kinase inhibitors.

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

recombinationsignaling

Input: Light

Implementation Constraints

cofactor dependency: cofactor requirement unknownencoding mode: genetically encodedimplementation constraint: context specific validationimplementation constraint: multi component delivery burdenimplementation constraint: spectral hardware requirementoperating role: regulatorswitch architecture: multi componentswitch architecture: recruitment

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

Claim 1correlationsupports2016Source 1needs review

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.
Claim 2correlationsupports2016Source 1needs review

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.
Claim 3correlationsupports2016Source 1needs review

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.
Claim 4correlationsupports2016Source 1needs review

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.
Claim 5correlationsupports2016Source 1needs review

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.
Claim 6correlationsupports2016Source 1needs review

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.
Claim 7correlationsupports2016Source 1needs review

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.
Claim 8correlationsupports2016Source 1needs review

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.
Claim 9correlationsupports2016Source 1needs review

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.
Claim 10correlationsupports2016Source 1needs review

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.
Claim 11correlationsupports2016Source 1needs review

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.
Claim 12correlationsupports2016Source 1needs review

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.
Claim 13correlationsupports2016Source 1needs review

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.
Claim 14correlationsupports2016Source 1needs review

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.
Claim 15correlationsupports2016Source 1needs review

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.
Claim 16correlationsupports2016Source 1needs review

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.
Claim 17correlationsupports2016Source 1needs review

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.
Claim 18dose dependent drug effectsupports2016Source 1needs review

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.
Claim 19dose dependent drug effectsupports2016Source 1needs review

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.
Claim 20dose dependent drug effectsupports2016Source 1needs review

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.
Claim 21dose dependent drug effectsupports2016Source 1needs review

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.
Claim 22dose dependent drug effectsupports2016Source 1needs review

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.
Claim 23dose dependent drug effectsupports2016Source 1needs review

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.
Claim 24dose dependent drug effectsupports2016Source 1needs review

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.
Claim 25dose dependent drug effectsupports2016Source 1needs review

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.
Claim 26dose dependent drug effectsupports2016Source 1needs review

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.
Claim 27dose dependent drug effectsupports2016Source 1needs review

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.
Claim 28dose dependent drug effectsupports2016Source 1needs review

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.
Claim 29dose dependent drug effectsupports2016Source 1needs review

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.
Claim 30dose dependent drug effectsupports2016Source 1needs review

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.
Claim 31dose dependent drug effectsupports2016Source 1needs review

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.
Claim 32dose dependent drug effectsupports2016Source 1needs review

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.
Claim 33dose dependent drug effectsupports2016Source 1needs review

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.
Claim 34dose dependent drug effectsupports2016Source 1needs review

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.
Claim 35drug effectsupports2016Source 1needs review

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.
Claim 36drug effectsupports2016Source 1needs review

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.
Claim 37drug effectsupports2016Source 1needs review

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.
Claim 38drug effectsupports2016Source 1needs review

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.
Claim 39drug effectsupports2016Source 1needs review

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.
Claim 40drug effectsupports2016Source 1needs review

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.
Claim 41drug effectsupports2016Source 1needs review

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.
Claim 42drug effectsupports2016Source 1needs review

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.
Claim 43drug effectsupports2016Source 1needs review

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.
Claim 44drug effectsupports2016Source 1needs review

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.
Claim 45drug effectsupports2016Source 1needs review

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.
Claim 46drug effectsupports2016Source 1needs review

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.
Claim 47drug effectsupports2016Source 1needs review

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.
Claim 48drug effectsupports2016Source 1needs review

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.
Claim 49drug effectsupports2016Source 1needs review

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.
Claim 50drug effectsupports2016Source 1needs review

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.
Claim 51drug effectsupports2016Source 1needs review

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.
Claim 52protein level effectsupports2016Source 1needs review

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.
Claim 53protein level effectsupports2016Source 1needs review

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.
Claim 54protein level effectsupports2016Source 1needs review

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.
Claim 55protein level effectsupports2016Source 1needs review

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.
Claim 56protein level effectsupports2016Source 1needs review

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.
Claim 57protein level effectsupports2016Source 1needs review

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.
Claim 58protein level effectsupports2016Source 1needs review

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.
Claim 59protein level effectsupports2016Source 1needs review

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.
Claim 60protein level effectsupports2016Source 1needs review

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.
Claim 61protein level effectsupports2016Source 1needs review

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.
Claim 62protein level effectsupports2016Source 1needs review

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.
Claim 63protein level effectsupports2016Source 1needs review

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.
Claim 64protein level effectsupports2016Source 1needs review

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.
Claim 65protein level effectsupports2016Source 1needs review

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.
Claim 66protein level effectsupports2016Source 1needs review

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.
Claim 67protein level effectsupports2016Source 1needs review

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.
Claim 68protein level effectsupports2016Source 1needs review

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.
Claim 69tool capabilitysupports2016Source 1needs review

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.
Claim 70tool capabilitysupports2016Source 1needs review

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.
Claim 71tool capabilitysupports2016Source 1needs review

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.
Claim 72tool capabilitysupports2016Source 1needs review

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.
Claim 73tool capabilitysupports2016Source 1needs review

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.
Claim 74tool capabilitysupports2016Source 1needs review

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.
Claim 75tool capabilitysupports2016Source 1needs review

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.
Claim 76tool capabilitysupports2016Source 1needs review

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.
Claim 77tool capabilitysupports2016Source 1needs review

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.
Claim 78tool capabilitysupports2016Source 1needs review

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.
Claim 79tool capabilitysupports2016Source 1needs review

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.
Claim 80tool capabilitysupports2016Source 1needs review

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.
Claim 81tool capabilitysupports2016Source 1needs review

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.
Claim 82tool capabilitysupports2016Source 1needs review

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.
Claim 83tool capabilitysupports2016Source 1needs review

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.
Claim 84tool capabilitysupports2016Source 1needs review

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.
Claim 85tool capabilitysupports2016Source 1needs review

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.
Claim 86tool functionsupports2016Source 1needs review

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
Claim 87tool functionsupports2016Source 1needs review

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
Claim 88tool functionsupports2016Source 1needs review

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
Claim 89tool functionsupports2016Source 1needs review

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
Claim 90tool functionsupports2016Source 1needs review

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
Claim 91tool functionsupports2016Source 1needs review

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
Claim 92tool functionsupports2016Source 1needs review

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
Claim 93tool functionsupports2016Source 1needs review

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
Claim 94tool functionsupports2016Source 1needs review

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
Claim 95tool functionsupports2016Source 1needs review

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
Claim 96tool functionsupports2016Source 1needs review

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
Claim 97tool functionsupports2016Source 1needs review

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
Claim 98tool functionsupports2016Source 1needs review

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
Claim 99tool functionsupports2016Source 1needs review

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
Claim 100tool functionsupports2016Source 1needs review

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
Claim 101tool functionsupports2016Source 1needs review

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
Claim 102tool functionsupports2016Source 1needs review

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.

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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

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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.

Compared with iLID/SspB

optoRAF and iLID/SspB address a similar problem space because they share recombination, signaling.

Shared frame: same top-level item type; shared target processes: recombination, signaling; shared mechanisms: heterodimerization; same primary input modality: light

Relative tradeoffs: appears more independently replicated; looks easier to implement in practice.

Compared with Opto-RhoGEFs

optoRAF and Opto-RhoGEFs address a similar problem space because they share recombination, signaling.

Shared frame: same top-level item type; shared target processes: recombination, signaling; shared mechanisms: heterodimerization; same primary input modality: light

optoRAF and single-component optogenetic tools for inducible RhoA GTPase signaling address a similar problem space because they share recombination, signaling.

Shared frame: same top-level item type; shared target processes: recombination, signaling; shared mechanisms: heterodimerization; same primary input modality: light

Ranked Citations

  1. 1.
    StructuralSource 1Scientific Reports2016Claim 11Claim 12Claim 11

    Extracted from this source document.