Toolkit Items

The active phytochrome binding (APB) domain is a protein interaction module present in most phytochrome-interacting factors (PIFs) that mediates binding to light-activated phytochrome B (phyB). In Arabidopsis PIF4 and PIF5, this domain is required for phyB-associated, phosphorylation-preceded, proteasome-sensitive degradation in a light-regulated shade-avoidance pathway.

Arabidopsis cryptochrome 2 (AtCRY2) is a blue-light-responsive plant photoreceptor domain that has been heterologously expressed in mammalian cells. In that context, blue light induces AtCRY2 photobody formation and also triggers AtCRY2 degradation, providing a light-controlled module linked to protein clustering and turnover.

Bacterial degraders are a proposed construct pattern for targeted protein degradation in bacteria. They are discussed as tools to interrogate protein function and as potential antimicrobial modalities.

Bacterial degrons are proteolysis-targeting signals that are appended to proteins to direct their degradation in bacterial cells. They are described as tools to interrogate and control protein function through targeted protein depletion.

The blue light-inducible degradation (B-LID) domain is a light-activated degron used to trigger loss of a fused protein in vivo. Available evidence indicates that it must be fused to the carboxy terminus of the target protein and can elicit light-dependent loss of Cactus function in developing Drosophila embryos.

The blue light-responsive Cas13b mRNA knockdown system is an optogenetic RNA-control platform in which blue light induces expression of an engineered Cas13b that specifically degrades target mRNAs. In the reported application, combining three blue light-inducible switches reduced protein levels by more than 99%.

CRISPRoff is an engineering method for light-induced degradation of single-guide RNA (sgRNA) that inactivates the CRISPR ribonucleoprotein. It enables spatiotemporal attenuation of CRISPR-Cas9 genome editing in cells through selective illumination.

Cry2 is a blue-light photoreceptor cryptochrome from Arabidopsis used as a light-responsive multi-component optogenetic switch. The supplied evidence supports blue-light-dependent photoactivation linked to regulation of transcription factor control and to CRY2 degradation.

The CRY2 and LOV-fused degron light-responsive repression/degradation system is a multi-component optogenetic platform reported in mammalian cells that uses light to simultaneously block transcription and deplete protein levels. It is based on Arabidopsis cryptochrome 2 (CRY2), which interacts with CIB1 upon illumination, together with a LOV-fused degron configuration.

CRY2-GFP is a C-terminal green fluorescent protein fusion of Arabidopsis cryptochrome 2 used to probe CRY2 blue-light responses. In the cited Plant Cell study, this fusion displayed constitutive biochemical and physiological activity and underwent blue-light-induced degradation more slowly than GFP-CRY2 or endogenous CRY2.

Deg-LITer is a multi-component optogenetic gene circuit in which the TetR repressor is fused to a degradation tag through the LOV2 light-sensitive domain. It is part of the LITer toolset for light-controlled regulation in mammalian cells.

The Destruction Complex is a Wnt signal transduction protein assembly that processes and promotes degradation of β-catenin. A 2022 study reported that nucleation of this assembly on the centrosome accelerates β-catenin degradation and changes Wnt-dependent human embryonic stem cell fate outcomes.

The combined EL222 and LOVdeg system is a light-responsive multi-component optogenetic system developed in Escherichia coli by pairing the existing EL222 module with the LOVdeg blue-light-inducible degradation tag. It is intended to enhance optogenetic performance by combining EL222-based control with post-translational light-inducible protein degradation.

Flash-Away is an intrabody-directed optogenetic protein degradation system that enables blue-light-triggered, targeted degradation of selected proteins. It has been reported to act on actin, MLKL, and ALFA-tagged proteins.

GFP-CRY2 is an N-terminal green fluorescent protein fusion to Arabidopsis CRY2. In the cited Plant Cell study, this fusion retained blue light-dependent biochemical and physiological activities similar to endogenous CRY2 and showed blue light-responsive degradation behavior more similar to native CRY2 than the reciprocal CRY2-GFP construct.

Light-Inducible Tuner (LITer) is a mammalian optogenetic gene-circuit platform in which TetR is fused through the LOV2 light-sensitive domain to either a Tet-inhibitory peptide or a degradation tag. It enables light-controlled negative-feedback regulation of gene expression and was reported to reduce expression noise while providing tunable output control.

The LOV2 domain-based optogenetic tool is a light-responsive protein-domain system reported to control protein degradation and cellular function. The supplied evidence identifies a LOV2-based optogenetic platform but does not specify the exact construct architecture or experimental context.

LOVdeg is an engineered protein tag that is appended to a protein of interest to enable blue-light-inducible degradation in Escherichia coli. It provides optically controlled post-translational regulation by coupling light exposure to loss of the tagged protein.

MALAT1 is a long noncoding RNA reported in trophoblasts to promote cell migration and invasion by reducing CRY2 protein abundance. In the cited study, MALAT1 recruits the E3 ubiquitin ligase FBXW7, impairing CRY2 protein stability and inducing ubiquitin-mediated CRY2 degradation.

Nanobody-mediated proteolysis-targeting chimeras are a degradation-based engineering method used in an optogenetically coordinated platform to regulate the intracellular factor Survivin in cancer cells. In the cited study context, they are combined with split-Cas9-based targeted gene editing for multi-level control of cancer cell fate.

opto-PROTAC is a light-inducible PROTAC design in which a photolabile caging group is installed on pomalidomide-based degraders to block activity in the dark and permit target protein degradation after ultraviolet A irradiation. It was demonstrated using caged pomalidomide and the PROTACs dBET1 and dALK to achieve spatiotemporal control of protein destruction.

Orthogonal degrons are bacterial construct patterns used in tunable degradation systems to direct targeted proteolysis of proteins of interest. The cited literature places them among recent advances that enable large screens and functional interrogation through regulated protein degradation.

pc-PROTAC1 is a photocaged PROTAC construct designed for light-dependent targeted protein degradation in live cells. In the cited study, it exhibited potent degradation activity only after light irradiation, establishing a light-activated degradation strategy.

pc-PROTAC3 is a photocaged PROTAC constructed against Bruton's tyrosine kinase (BTK) within a light-inducible protein degradation strategy. The available evidence states that this approach was successfully applied to generate pc-PROTAC3 and that photocaged PROTACs can activate degradation activity upon light exposure.

Photo-caged PROTACs (pc-PROTACs) are light-activated proteolysis-targeting chimeras designed to trigger targeted protein degradation only after irradiation. The reported study presented pc-PROTACs as a general strategy for inducing degradation activity with light and showed that pc-PROTAC1 was potently active in live cells only after light exposure.

The photo-N-degron is a peptide tag for optogenetic control of protein function in vivo through light-mediated protein degradation. It was reported to direct light-dependent degradation in Saccharomyces cerevisiae and Drosophila melanogaster, including light-dependent loss of Cactus function in developing Drosophila embryos.

The photosensitive degron (psd) is a protein-domain tool that confers acute light-induced degradation on fused proteins. Available evidence indicates activity in the nervous system and a construct requirement that the psd be placed at the carboxy terminus of the target protein.

Split-Cas9-based targeted gene editing is a gene-editing component used in an optogenetically coordinated platform with nanobody-mediated proteolysis-targeting chimeras. In the reported application, it was used to regulate Survivin as part of a multi-level strategy to control cancer cell fate.

This entry refers broadly to imaging-oriented tools and sensors associated with bacterial degron and degrader concepts. The supplied evidence only states that bacterial degrons can be used to interrogate and control protein function and mentions “tools and sensors for imaging,” without defining a specific construct, sensor architecture, or imaging readout.

The TRIM21 RING domain is a catalytic protein domain whose ubiquitination activity is activated by substrate-induced clustering that promotes intermolecular RING dimerization. In the cited 2020 study, this activation mechanism underlies TRIM21-dependent antiviral responses and Trim-Away-mediated protein degradation.

TRIM21-nanobody chimeras are engineered Trim-Away constructs that fuse TRIM21 activity to nanobody-based target recognition. In the cited 2020 work, these chimeras were described as highly active and were further adapted for optogenetic control of targeted protein degradation.