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Related Concept Videos

Regulated Protein Degradation02:58

Regulated Protein Degradation

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It is vital to regulate the activity of enzymatic as well as non-enzymatic proteins inside the cell. This can be achieved either through creating a balance between their rate of synthesis and degradation or regulating the intrinsic activity of the protein. Both these regulation mechanisms play an essential role in the normal functioning of cells.
Protein degradation plays two important roles in the cells. It helps to protect cells from misfolded or damaged proteins before they lead to a...
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Eukaryotic cells can degrade proteins through several pathways. One of the most important among these is the ubiquitin-proteasome pathway. It helps the cell eliminate the misfolded, damaged, or unwarranted cytoplasmic proteins in a highly specific manner.
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G protein-coupled receptor (GPCR) signaling plays a crucial role in cell functioning. GPCR desensitization is an equally essential process. It allows cells to respond to changing environments and regain sensitivity to new stimuli while preventing unnecessary stimulation when no longer needed. Prolonged exposure to stimuli leads to GPCR desensitization. It involves blocking the receptors from binding and activating additional G proteins. This inhibits activation of downstream effectors, thereby...
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Updated: Sep 9, 2025

High-Throughput Cellular Profiling of Targeted Protein Degradation Compounds Using HiBiT CRISPR Cell Lines
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Reductively activated CPP-PROTAC nanocomplexes enhance target degradation via efficient cellular uptake.

Maho Miyamoto1,2, Kosuke Saito3, Hidetomo Yokoo2

  • 1Graduate School of Medical Life Science, Yokohama City University 1-7-29 Yokohama 230-0045 Japan.

RSC Chemical Biology
|September 2, 2025
PubMed
Summary
This summary is machine-generated.

We created a nanoparticle using a cell-penetrating peptide-PROTAC conjugate (MZ1-R9) and dextran sulfate to enhance targeted protein degradation. This delivery system improves PROTAC bioavailability and overcomes cell membrane challenges.

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Area of Science:

  • Biotechnology
  • Molecular Biology
  • Drug Delivery Systems

Background:

  • Targeted protein degradation is a promising therapeutic strategy.
  • Conventional Proteolysis Targeting Chimeras (PROTACs) face challenges with cellular uptake and bioavailability.
  • Developing effective delivery systems is crucial for PROTAC efficacy.

Purpose of the Study:

  • To develop a novel nanoparticle delivery platform for PROTACs.
  • To enhance cellular uptake and efficiency of BRD4 degradation using a PROTAC conjugate.
  • To improve PROTAC bioavailability and overcome membrane permeability barriers.

Main Methods:

  • Conjugation of a cell-penetrating peptide (R9) and a PROTAC (MZ1) via a disulfide linker.
  • Encapsulation of the MZ1-R9 conjugate within a dextran sulfate nanoparticle.
  • Evaluation of cellular uptake and BRD4 degradation in target cells.

Main Results:

  • The MZ1-R9 nanoparticle demonstrated enhanced cellular uptake compared to the free PROTAC.
  • Significant BRD4 degradation was observed in cells treated with the nanoparticle.
  • Improved PROTAC bioavailability and efficacy were achieved with the nanoparticle delivery system.

Conclusions:

  • The developed nanoparticle platform effectively delivers PROTACs into cells.
  • This strategy enhances targeted protein degradation by overcoming membrane permeability issues.
  • The nanoparticle-based delivery of MZ1-R9 shows significant promise for therapeutic applications in targeted protein degradation.