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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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The Proteasome02:18

The Proteasome

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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.
In this pathway, the target proteins are first tagged with small proteins called ubiquitin. A series of enzymes carry out the ubiquitination of the target proteins - E1 (ubiquitin-activating enzyme), E2 (ubiquitin-conjugating enzyme), and E3...
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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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Protein Complexes with Interchangeable Parts01:57

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Groups of proteins may form a complex where each protein in this complex has a different role in the overall execution of the complex’s function. Often some of the proteins in the complex can be replaced by a closely related variant to give a complex that contains many of the same components yet is functionally distinct.
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Proteins: From Genes to Degradation02:11

Proteins: From Genes to Degradation

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Within a biological system, the DNA encodes the RNA, and the nucleotide sequence in the RNA further defines the amino acid sequence in the protein. This is referred to as “The Central Dogma of Molecular Biology” - a term coined by Francis Crick.  Central dogma is a firm principle in biology that defines the flow of genetic information within any life form. The two fundamental steps in central dogma are - transcription and translation.
Transcription is the synthesis of RNA...
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The Proteasome Structure01:17

The Proteasome Structure

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The ubiquitin-proteasome pathway is a well-known mechanism utilized by eukaryotic cells to remove cytoplasmic proteins that are misfolded, damaged, or no longer needed. In this pathway, the protein that needs to be eliminated undergoes a process called ubiquitination, where a chain of ubiquitin molecules is attached to the 48th lysine residue of the target protein. This ubiquitin modification helps the proteasome distinguish between a target protein and a healthy protein.
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Updated: Sep 27, 2025

High-Throughput Cellular Profiling of Targeted Protein Degradation Compounds Using HiBiT CRISPR Cell Lines
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Multifaceted targeted protein degradation systems for different cellular compartments.

Cornelia E Zorca1, Armaan Fallahi1, Sophie Luo1

  • 1Department of Neurology and Neurosurgery, Montreal Neurological Institute, McGill University, Montreal, Quebec, Canada.

Bioessays : News and Reviews in Molecular, Cellular and Developmental Biology
|April 13, 2022
PubMed
Summary

Targeted protein degradation (TPD) offers new therapeutic strategies by hijacking cellular machinery to eliminate disease-causing proteins. This review explores diverse TPD tools, from PROTACs to LYTACs, for precise disease treatment.

Keywords:
lysosomal degradationproteasometargeted protein degradationubiquitin

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Area of Science:

  • Biochemistry
  • Molecular Biology
  • Drug Discovery

Background:

  • Cellular homeostasis relies on selective protein degradation.
  • Dysregulation of protein degradation is implicated in various diseases.
  • Targeted protein degradation (TPD) leverages cellular pathways for therapeutic protein level regulation.

Purpose of the Study:

  • To review the expanding toolkit of TPD strategies.
  • To discuss TPD methods acting at different levels of gene expression and cellular compartments.
  • To highlight the clinical potential of TPD in disease treatment.

Main Methods:

  • Review of proteolysis targeting chimeras (PROTACs) and dephosphorylation targeting chimeras (DEPTACs) for proteasome-mediated degradation.
  • Overview of autophagy-targeting chimeras (AUTACs), autophagosome tethering compounds (ATTECs), and lysosome targeting chimeras (LYTACs) for lysosomal degradation.
  • Discussion of ribonuclease targeting chimeras (RIBOTACs) and transcription factor targeting chimeras (TRAFTACs) for upstream gene expression control.

Main Results:

  • A diverse array of TPD tools is available, targeting proteins, RNAs, and transcription factors.
  • These tools offer precise control over protein levels via the proteasome or lysosome.
  • TPD methods provide opportunities for therapeutic intervention throughout the gene expression pathway.

Conclusions:

  • TPD approaches represent a significant advancement in therapeutic strategies.
  • The reviewed TPD tools offer versatile applications for diverse disease contexts.
  • Further development and clinical investigation of TPD are warranted for effective disease management.