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Related Concept Videos

The Proteasome01:13

The Proteasome

1.5K
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.
In this pathway, the target proteins are first tagged with small proteins called ubiquitin. This involves participation of a series of enzymes including— E1 (ubiquitin-activating enzyme), E2 (ubiquitin-conjugating enzyme), and E3...
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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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The Proteasome02:18

The Proteasome

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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.
The proteasome is an...
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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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Regulated Protein Degradation02:58

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Ubiquitin Chain Analysis by Parallel Reaction Monitoring
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Multi-Step Ubiquitin Decoding Mechanism for Proteasomal Degradation.

Hikaru Tsuchiya1, Akinori Endo1, Yasushi Saeki1

  • 1Protein Metabolism Project, Tokyo Metropolitan Institute of Medical Science, Tokyo 156-8506, Japan.

Pharmaceuticals (Basel, Switzerland)
|June 27, 2020
PubMed
Summary
This summary is machine-generated.

The 26S proteasome degrades ubiquitylated proteins, crucial for cell homeostasis. This review highlights the link between p97, shuttling factors, and the proteasome for efficient degradation and proteasome mobility.

Keywords:
liquid–liquid phase separationp97/VCPproteasomal ubiquitin receptorsproteasomeprotein degradationubiquitin

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Area of Science:

  • Cell Biology
  • Molecular Biology
  • Biochemistry

Background:

  • The 26S proteasome is essential for regulated protein degradation in eukaryotic cells, accounting for ~70% of cellular proteolysis.
  • Ubiquitylation targets proteins for proteasomal degradation, with an expanding understanding of ubiquitin chain linkages beyond Lys48.
  • Cellular proteostasis relies on the proteasome, and its dysfunction can disrupt cell homeostasis.

Purpose of the Study:

  • To review the emerging role of the p97/VCP chaperone and substrate-shuttling factors in facilitating proteasomal degradation.
  • To highlight the spatiotemporal regulation and mobility of proteasomes in response to cellular stress.
  • To present evidence for proteasome-containing nuclear foci formation via liquid-liquid phase separation.

Main Methods:

  • Literature review focusing on the interplay between p97, shuttling factors, and the 26S proteasome.
  • Analysis of ubiquitin chain diversity and its implications for proteasomal targeting.
  • Examination of proteasome dynamics and localization, including stress-induced nuclear foci formation.

Main Results:

  • A key link exists between the AAA-ATPase p97/VCP, substrate-shuttling factors, and the 26S proteasome for efficient protein degradation.
  • Proteasomal degradation pathways involve diverse ubiquitin linkages and can require extraction/segregation by p97.
  • Proteasomes exhibit dynamic mobility and form nuclear foci through liquid-liquid phase separation under hyperosmotic stress.

Conclusions:

  • The p97-shuttling factor-proteasome axis is critical for efficient and regulated protein turnover.
  • Understanding ubiquitin code expansion and proteasome dynamics is vital for comprehending cellular proteostasis.
  • Liquid-liquid phase separation offers a mechanism for proteasome compartmentalization during cellular stress.