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Related Concept Videos

The Proteasome Structure01:17

The Proteasome Structure

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...
The Proteasome02:18

The Proteasome

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...
The Proteasome01:13

The Proteasome

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 (ubiquitin...
The Proteasome02:18

The Proteasome

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...
Covalently Linked Protein Regulators02:04

Covalently Linked Protein Regulators

Proteins can undergo many types of post-translational modifications, often in response to changes in their environment. These modifications play an important role in the function and stability of these proteins. Covalently linked molecules include functional groups, such as methyl, acetyl, and phosphate groups, and also small proteins, such as ubiquitin. There are around 200 different types of covalent regulators that have been identified.
These groups modify specific amino acids in a protein.
Regulated Protein Degradation02:58

Regulated Protein Degradation

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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Related Experiment Video

Updated: Jun 9, 2026

Quantifying Subcellular Ubiquitin-proteasome Activity in the Rodent Brain
09:25

Quantifying Subcellular Ubiquitin-proteasome Activity in the Rodent Brain

Published on: May 21, 2019

Parkin directly modulates 26S proteasome activity.

Ji Won Um1, Eunju Im, Hyun Jung Lee

  • 1Department of Biology, College of Life Science and Biotechnology, Yonsei University, Seoul, Korea.

The Journal of Neuroscience : the Official Journal of the Society for Neuroscience
|September 3, 2010
PubMed
Summary

Parkinson's disease involves protein buildup and neuron loss. The parkin protein, crucial for proteasome function, activates it independently of its E3 ligase role, suggesting mutations contribute to PD's proteasomal dysfunction.

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Time-Lapse Video Microscopy for Assessment of EYFP-Parkin Aggregation as a Marker for Cellular Mitophagy
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Time-Lapse Video Microscopy for Assessment of EYFP-Parkin Aggregation as a Marker for Cellular Mitophagy

Published on: May 4, 2016

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Last Updated: Jun 9, 2026

Quantifying Subcellular Ubiquitin-proteasome Activity in the Rodent Brain
09:25

Quantifying Subcellular Ubiquitin-proteasome Activity in the Rodent Brain

Published on: May 21, 2019

Time-Lapse Video Microscopy for Assessment of EYFP-Parkin Aggregation as a Marker for Cellular Mitophagy
09:29

Time-Lapse Video Microscopy for Assessment of EYFP-Parkin Aggregation as a Marker for Cellular Mitophagy

Published on: May 4, 2016

Area of Science:

  • Neuroscience
  • Molecular Biology
  • Genetics

Background:

  • Parkinson's disease (PD) is a neurodegenerative disorder characterized by dopaminergic neuron loss.
  • Abnormal protein aggregation is a hallmark of both sporadic and familial PD.
  • Proteasome dysfunction is implicated in PD pathogenesis, with parkin gene mutations linked to familial forms.

Purpose of the Study:

  • To investigate the role of the parkin protein in 26S proteasome regulation.
  • To determine if parkin's E3 ubiquitin ligase activity is necessary for proteasome activation.
  • To elucidate the mechanism by which parkin interacts with and modulates proteasome function.

Main Methods:

  • Biochemical assays to assess parkin's effect on 26S proteasome activity.
  • Analysis of parkin's interaction with 19S proteasomal subunits.
  • Site-directed mutagenesis to study the role of the N-terminal ubiquitin-like domain and PD-linked mutations (e.g., R42P).

Main Results:

  • Parkin activates the 26S proteasome in a manner independent of its E3 ubiquitin ligase activity.
  • The N-terminal ubiquitin-like domain of parkin is essential for this activation.
  • Parkin enhances the interaction between 19S proteasomal subunits.
  • The Parkinson's disease-linked R42P mutant of parkin fails to activate the 26S proteasome.

Conclusions:

  • Parkin plays a novel role in 26S proteasome assembly and function.
  • Parkin's ability to activate the proteasome is linked to its interaction with proteasomal subunits, not its E3 ligase activity.
  • Mutations in parkin, such as R42P, can lead to proteasomal dysfunction, contributing to Parkinson's disease pathogenesis.