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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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Receptor-mediated Endocytosis01:39

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Overview
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Export of Misfolded Proteins out of the ER01:32

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After folding, the ER assesses the quality of secretory and membrane proteins. The correctly folded proteins are cleared by the calnexin cycle for transport to their final destination, while misfolded proteins are held back in the ER lumen. The ER chaperones attempt to unfold and refold the misfolded proteins but sometimes fail to achieve the correct native conformation. Such terminally misfolded proteins are then exported to the cytosol by ER-associated degradation or ERAD pathway for...
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Receptor Downregulation in MVBs01:15

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Multivesicular bodies (MVBs) are mature endosomes that sort ubiquitinated proteins and then fuse with lysosomes to degrade the sorted proteins. Epidermal growth factor (EGF) and its receptor (EGFR) form a complex that can be internalized through endocytosis, sorted into an MVB, and later degraded.
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The Proteasome02:18

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Eukaryotic cells can degrade proteins through several pathways. One of the most important amongst 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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Essential proteins such as insulin or low-density lipoprotein (LDL) and micronutrients such as iron enter a eukaryotic cell through receptor-mediated endocytosis. Subsequently, the early endosomes fuse with the vesicles containing such receptor-ligand complexes and play a vital role in sorting the incoming ligands and receptors. While the ligands are either degraded inside the vesicle or released into the cytosol, their receptors are returned to the plasma membrane for further rounds of...
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Updated: Jul 15, 2025

High-Throughput Cellular Profiling of Targeted Protein Degradation Compounds Using HiBiT CRISPR Cell Lines
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Designed Endocytosis-Triggering Proteins mediate Targeted Degradation.

Buwei Huang1,2,3, Mohamad Abedi1,2, Green Ahn4

  • 1Department of Biochemistry, University of Washington, Seattle, WA, USA.

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|October 2, 2023
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Summary

Researchers developed novel endocytosis-triggering binding proteins (EndoTags) for targeted protein degradation. These genetically encodable EndoTags overcome limitations of existing methods and offer therapeutic potential for various applications.

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Area of Science:

  • Biochemistry
  • Molecular Biology
  • Drug Discovery

Background:

  • Cell surface receptor endocytosis and lysosomal trafficking are crucial biological processes.
  • Existing therapeutic strategies like LYTAC and KineTAC utilize modified ligands for targeted protein degradation but face limitations such as ligand competition and manufacturing complexities.
  • The absence of natural ligands for certain receptors hinders the development of targeted degradation therapies.

Conclusions:

  • Genetically encodable EndoTags provide a versatile and modular platform for targeted protein degradation, overcoming limitations of existing ligand-based approaches.
  • EndoTags facilitate receptor-mediated endocytosis and lysosomal degradation, offering potential for tissue-specific therapies.
  • The tunability and design flexibility of EndoTags hold significant promise for targeted degradation, signaling pathway activation, and enhanced cellular uptake in drug and nucleic acid conjugates.