Genetically Encoded Sensor Cells for the Screening of Glucocorticoid Receptor (GR) Effectors in Herbal Extracts

Kang, Chung Nam; Kim, Soyoun; Lee, Euiyeon; Ryu, Jeahee; Lee, Minhyung; Kwon, Youngeun

doi:10.3390/bios11090341

Cited by 5 publications

(4 citation statements)

References 53 publications

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“…In some cases, more thorough investigations included analysis of effects on GR expression, major steps in GR activation: its phosphorylation (mostly at activating Ser211) and nuclear translocation; and GR ligand properties assessed by molecular docking or ligand-binding assays [87][88][89][90][91][92][93][94]. Recently, focused screens for natural mimetics of cortisol were performed utilizing genetically engineered sensor cells detecting GR nuclear translocation, which demonstrated that decursin from Dong quai (Angelica sinensis, commonly known as female ginseng), and L-limonene from peppermint oil induce GR translocation similar to cortisol [95,96].…”

Section: Natural Compounds With Segram Propertiesmentioning

confidence: 99%

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The long winding road to the safer glucocorticoid receptor (GR) targeting therapies

et al. 2022

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Glucocorticoids (Gcs) are widely used to treat inflammatory diseases and hematological malignancies, and despite the introduction of novel anti-inflammatory and anti-cancer biologics, the use of inexpensive and effective Gcs is expected to grow. Unfortunately, chronic treatment with Gcs results in multiple atrophic and metabolic side effects. Thus, the search for safer glucocorticoid receptor (GR)-targeted therapies that preserve therapeutic potential of Gcs but result in fewer adverse effects remains highly relevant. Development of selective GR agonists/modulators (SEGRAM) with reduced side effects, based on the concept of dissociation of GR transactivation and transrepression functions, resulted in limited success, and currently focus has shifted towards partial GR agonists. Additional approach is the identification and inhibition of genes associated with Gcs specific side effects. Others and we recently identified GR target genes REDD1 and FKBP51 as key mediators of Gcs-induced atrophy, and selected and validated candidate molecules for REDD1 blockage including PI3K/Akt/mTOR inhibitors. In this review, we summarized classic and contemporary approaches to safer GR-mediated therapies including unique concept of Gcs combination with REDD1 inhibitors. We discussed protective effects of REDD1 inhibitors against Gcs–induced atrophy in skin and bone and underlined the translational potential of this combination for further development of safer and effective Gcs-based therapies.

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Section: Natural Compounds With Segram Propertiesmentioning

confidence: 99%

“…The SEGRAM activity of these biomolecules was assessed not only in human cell lines, but in some cases in vivo in zebrafish larvae model and in rodents ( [87,95,98,100,[102][103][104][105][106] and [99,101,107,108], respectively).…”

Section: Natural Compounds With Segram Propertiesmentioning

confidence: 99%

The long winding road to the safer glucocorticoid receptor (GR) targeting therapies

et al. 2022

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“…Similarly, the intein-mediated conditional protein splicing (CPS) reaction has become an important strategy for protein engineering [ 45 , 46 ]. The intein-mediated split NLS and NES has also been applied for building translocation-based biosensors [ 47 , 48 ]. Essentially, the split signal peptide (NLS or NES) is fused to a FP serves as a reporter.…”

Section: Framework For Engineering Genetically Encoded Plant-based Bi...mentioning

confidence: 99%

Biological and Molecular Components for Genetically Engineering Biosensors in Plants

et al. 2022

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Plants adapt to their changing environments by sensing and responding to physical, biological, and chemical stimuli. Due to their sessile lifestyles, plants experience a vast array of external stimuli and selectively perceive and respond to specific signals. By repurposing the logic circuitry and biological and molecular components used by plants in nature, genetically encoded plant-based biosensors (GEPBs) have been developed by directing signal recognition mechanisms into carefully assembled outcomes that are easily detected. GEPBs allow for in vivo monitoring of biological processes in plants to facilitate basic studies of plant growth and development. GEPBs are also useful for environmental monitoring, plant abiotic and biotic stress management, and accelerating design-build-test-learn cycles of plant bioengineering. With the advent of synthetic biology, biological and molecular components derived from alternate natural organisms (e.g., microbes) and/or de novo parts have been used to build GEPBs. In this review, we summarize the framework for engineering different types of GEPBs. We then highlight representative validated biological components for building plant-based biosensors, along with various applications of plant-based biosensors in basic and applied plant science research. Finally, we discuss challenges and strategies for the identification and design of biological components for plant-based biosensors.

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“…Cell-based optical biosensors have emerged as a powerful tool for screening biological effectors for various receptors as they can monitor biological interactions in their native context where their biological actions are taking place [ 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 ]. Sensor cells are generated by genetically encoding sensor proteins that contain a molecular recognition element as well as a reporter element.…”

Section: Introductionmentioning

confidence: 99%

Cell-Based Sensors for the Detection of EGF and EGF-Stimulated Ca2+ Signaling

et al. 2023

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Epidermal growth factor (EGF)-mediated activation of EGF receptors (EGFRs) has become an important target in drug development due to the implication of EGFR-mediated cellular signaling in cancer development. While various in vitro approaches are developed for monitoring EGF-EGFR interactions, they have several limitations. Herein, we describe a live cell-based sensor system that can be used to monitor the interaction of EGF and EGFR as well as the subsequent signaling events. The design of the EGF-detecting sensor cells is based on the split-intein-mediated conditional protein trans-cleavage reaction (CPC). CPC is triggered by the presence of the target (EGF) to activate a signal peptide that translocates the fluorescent cargo to the target cellular location (mitochondria). The developed sensor cell demonstrated excellent sensitivity with a fast response time. It was also successfully used to detect an agonist and antagonist of EGFR (transforming growth factor-α and Cetuximab, respectively), demonstrating excellent specificity and capability of screening the analytes based on their function. The usage of sensor cells was then expanded from merely detecting the presence of target to monitoring the target-mediated signaling cascade, by exploiting previously developed Ca2+-detecting sensor cells. These sensor cells provide a useful platform for monitoring EGF-EGFR interaction, for screening EGFR effectors, and for studying downstream cellular signaling cascades.

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Genetically Encoded Sensor Cells for the Screening of Glucocorticoid Receptor (GR) Effectors in Herbal Extracts

Cited by 5 publications

References 53 publications

The long winding road to the safer glucocorticoid receptor (GR) targeting therapies

The long winding road to the safer glucocorticoid receptor (GR) targeting therapies

Biological and Molecular Components for Genetically Engineering Biosensors in Plants

Cell-Based Sensors for the Detection of EGF and EGF-Stimulated Ca2+ Signaling

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