Jove
Visualize
Contact Us
JoVE
x logofacebook logolinkedin logoyoutube logo
ABOUT JoVE
OverviewLeadershipBlogJoVE Help Center
AUTHORS
Publishing ProcessEditorial BoardScope & PoliciesPeer ReviewFAQSubmit
LIBRARIANS
TestimonialsSubscriptionsAccessResourcesLibrary Advisory BoardFAQ
RESEARCH
JoVE JournalMethods CollectionsJoVE Encyclopedia of ExperimentsArchive
EDUCATION
JoVE CoreJoVE BusinessJoVE Science EducationJoVE Lab ManualFaculty Resource CenterFaculty Site
Terms & Conditions of Use
Privacy Policy
Policies

Related Concept Videos

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...
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.
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...
Export of Misfolded Proteins out of the ER01:32

Export of Misfolded Proteins out of the ER

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...
Tail-anchoring of Proteins in the ER Membrane01:45

Tail-anchoring of Proteins in the ER Membrane

Tail-anchored, or TA, proteins are estimated to make up to 3-5% of membrane proteins found in the eukaryotic cell. Such proteins have a single transmembrane domain located approximately 30 amino acid residues upstream from the C-terminal end. As a result, the signal recognition particle (SRP) cannot guide a TA protein to the ER membrane for cotranslational insertion. Hence, they are integrated into the ER membrane post-translationally using their C-terminal end as the anchor. TA proteins...

You might also read

Related Articles

Articles linked to this work by shared authors, journal, and citation graph.

Sort by
Same author

CLN5 disease-causing mutations impact lysosomal biology by affecting intracellular degradation and protein trafficking.

Biochimica et biophysica acta. Molecular basis of disease·2026
Same author

Determining Lysosomal Enzyme Activity Using Fluorogenic Probes.

Methods in molecular biology (Clifton, N.J.)·2025
Same author

Phosphorylation on serine 72 modulates Rab7A palmitoylation and retromer recruitment.

Journal of cell science·2024
Same author

The Batten disease protein CLN3 is important for stress granules dynamics and translational activity.

The Journal of biological chemistry·2023
Same author

Mechanisms regulating the sorting of soluble lysosomal proteins.

Bioscience reports·2022
Same author

Autophagy in the Neuronal Ceroid Lipofuscinoses (Batten Disease).

Frontiers in cell and developmental biology·2022

Related Experiment Video

Updated: May 13, 2026

Comparative Strategies for Ubiquitination Detection in Mammalian Cell Lysates Using SMAD2/SMURF2 as a Model
09:00

Comparative Strategies for Ubiquitination Detection in Mammalian Cell Lysates Using SMAD2/SMURF2 as a Model

Published on: April 17, 2026

Sortilin turnover is mediated by ubiquitination.

Karine Dumaresq-Doiron1, Felix Jules, Stephane Lefrancois

  • 1Centre de recherche de l'Hôpital Maisonneuve-Rosemont, Université de Montréal, Montréal, QC, Canada H1T 2M4.

Biochemical and Biophysical Research Communications
|March 15, 2013
PubMed
Summary

Palmitoylation prevents sortilin degradation, while ubiquitination targets it for lysosomal breakdown via the ESCRT pathway. Nedd4 ligase mediates this, balancing receptor levels and lysosomal sorting.

More Related Videos

In Vitro Ubiquitination and Deubiquitination Assays of Nucleosomal Histones
11:36

In Vitro Ubiquitination and Deubiquitination Assays of Nucleosomal Histones

Published on: July 25, 2019

Evaluation of Substrate Ubiquitylation by E3 Ubiquitin-ligase in Mammalian Cell Lysates
09:47

Evaluation of Substrate Ubiquitylation by E3 Ubiquitin-ligase in Mammalian Cell Lysates

Published on: May 10, 2022

Related Experiment Videos

Last Updated: May 13, 2026

Comparative Strategies for Ubiquitination Detection in Mammalian Cell Lysates Using SMAD2/SMURF2 as a Model
09:00

Comparative Strategies for Ubiquitination Detection in Mammalian Cell Lysates Using SMAD2/SMURF2 as a Model

Published on: April 17, 2026

In Vitro Ubiquitination and Deubiquitination Assays of Nucleosomal Histones
11:36

In Vitro Ubiquitination and Deubiquitination Assays of Nucleosomal Histones

Published on: July 25, 2019

Evaluation of Substrate Ubiquitylation by E3 Ubiquitin-ligase in Mammalian Cell Lysates
09:47

Evaluation of Substrate Ubiquitylation by E3 Ubiquitin-ligase in Mammalian Cell Lysates

Published on: May 10, 2022

Area of Science:

  • Cell biology
  • Molecular trafficking
  • Protein post-translational modifications

Background:

  • Sortilin directs cargo from the Golgi to lysosomes, with some degradation occurring over time.
  • Palmitoylation of sortilin was recently found to prevent lysosomal degradation and promote Golgi recycling.

Purpose of the Study:

  • To investigate the degradation pathway of non-palmitoylated sortilin.
  • To identify the E3 ubiquitin ligase responsible for sortilin ubiquitination.
  • To elucidate the opposing roles of palmitoylation and ubiquitination in sortilin regulation.

Main Methods:

  • Analysis of sortilin ubiquitination and lysosomal internalization.
  • Investigation of the ESCRT pathway's role in sortilin degradation.
  • Identification of E3 ubiquitin ligases using biochemical assays.

Main Results:

  • Non-palmitoylated sortilin undergoes ubiquitination and lysosomal degradation via the ESCRT pathway.
  • Nedd4 was identified as the E3 ubiquitin ligase mediating sortilin ubiquitination.
  • Palmitoylation and ubiquitination act antagonistically to control sortilin stability and lysosomal trafficking.

Conclusions:

  • Sortilin degradation is regulated by a balance between palmitoylation and Nedd4-mediated ubiquitination.
  • This regulatory mechanism controls the amount of sortilin and its cargo delivered to lysosomes.
  • The findings reveal a novel control point for intracellular sorting and protein turnover.