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

The Proteasome01:13

The Proteasome

1.9K
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...
1.9K
The Proteasome02:18

The Proteasome

10.4K
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...
10.4K
Export of Misfolded Proteins out of the ER01:32

Export of Misfolded Proteins out of the ER

5.4K
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...
5.4K
Lysosomal Hydrolases01:22

Lysosomal Hydrolases

4.7K
Lysosomes are the site for the degradation of macromolecules and biological polymers released during membrane trafficking events such as secretory, endocytic, autophagic, and phagocytic pathways. The membrane-enclosed area of the lysosome, called the lumen, contains hydrolytic enzymes active in an acidic environment. These acid hydrolases are functional at a pH between 4.5 and 5 and are involved in cellular processes such as cell signaling, energy metabolism, restoration of the plasma membrane,...
4.7K
Protein Complex Assembly02:41

Protein Complex Assembly

17.0K
Proteins can form homomeric complexes with another unit of the same protein or heteromeric complexes with different types.  Most protein complexes self-assemble spontaneously via ordered pathways, while some proteins need assembly factors that guide their proper assembly. Despite the crowded intracellular environment, proteins usually interact with their correct partners and form functional complexes.
Many viruses self-assemble into a fully functional unit using the infected host cell to...
17.0K
Molecular Chaperones and Protein Folding03:00

Molecular Chaperones and Protein Folding

20.6K
The native conformation of a protein is formed by interactions between the side chains of its constituent amino acids. When the amino acids cannot form these interactions, the protein cannot fold by itself and needs chaperones. Notably, chaperones do not relay any additional information required for the folding of polypeptides; the native conformation of a protein is determined solely by its amino acid sequence. Chaperones catalyze protein folding without being a part of the folded protein.
The...
20.6K

You might also read

Related Articles

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

Sort by
Same author

N-SREBP2 Provides a Mechanism for Dynamic Control of Cellular Cholesterol Homeostasis.

Cells·2024
Same author

Eupatilin improves cilia defects in human CEP290 ciliopathy models.

bioRxiv : the preprint server for biology·2023
Same author

The immune cell infiltrate in the tumour microenvironment of phaeochromocytomas and paragangliomas.

Endocrine-related cancer·2022
Same author

Mechanical loading inhibits cartilage inflammatory signalling via an HDAC6 and IFT-dependent mechanism regulating primary cilia elongation.

Osteoarthritis and cartilage·2019
Same author

The effectiveness and safety of biological therapeutics in juvenile-onset systemic lupus erythematosus (JSLE): a systematic review.

Lupus·2018
Same author

A novel missense mutation in HSF4 causes autosomal-dominant congenital lamellar cataract in a British family.

Eye (London, England)·2017

Related Experiment Video

Updated: Mar 7, 2026

Generation of Native, Untagged Huntingtin Exon1 Monomer and Fibrils Using a SUMO Fusion Strategy
11:22

Generation of Native, Untagged Huntingtin Exon1 Monomer and Fibrils Using a SUMO Fusion Strategy

Published on: June 27, 2018

8.5K

Hsp40 Molecules That Target to the Ubiquitin-proteasome System Decrease Inclusion Formation in Models of

J L Howarth1, S Kelly1, M P Keasey1

  • 1Henry Wellcome Laboratories for Integrated Neuroscience and Endocrinology, University of Bristol, Bristol, UK.

Molecular Therapy : the Journal of the American Society of Gene Therapy
|February 10, 2017
PubMed
Summary

Heat shock protein HSJ1a and HSJ1b reduce harmful protein inclusions in polyglutamine diseases like spinal and bulbar muscular atrophy by enhancing protein degradation via the ubiquitin-proteasome system.

More Related Videos

Fractionation for Resolution of Soluble and Insoluble Huntingtin Species
07:08

Fractionation for Resolution of Soluble and Insoluble Huntingtin Species

Published on: February 27, 2018

10.1K
Assays for the Degradation of Misfolded Proteins in Cells
10:56

Assays for the Degradation of Misfolded Proteins in Cells

Published on: August 28, 2016

12.6K

Related Experiment Videos

Last Updated: Mar 7, 2026

Generation of Native, Untagged Huntingtin Exon1 Monomer and Fibrils Using a SUMO Fusion Strategy
11:22

Generation of Native, Untagged Huntingtin Exon1 Monomer and Fibrils Using a SUMO Fusion Strategy

Published on: June 27, 2018

8.5K
Fractionation for Resolution of Soluble and Insoluble Huntingtin Species
07:08

Fractionation for Resolution of Soluble and Insoluble Huntingtin Species

Published on: February 27, 2018

10.1K
Assays for the Degradation of Misfolded Proteins in Cells
10:56

Assays for the Degradation of Misfolded Proteins in Cells

Published on: August 28, 2016

12.6K

Area of Science:

  • Neuroscience
  • Molecular Biology
  • Genetics

Background:

  • Polyglutamine diseases are characterized by the formation of toxic protein inclusions.
  • Heat shock proteins (HSPs) are known to play roles in protein folding and degradation.
  • The specific mechanisms by which HSPs, particularly DnaJ-like-1 (HSJ1) proteins, affect polyglutamine-mediated inclusion formation require further elucidation.

Purpose of the Study:

  • To investigate the efficacy of heat shock proteins, including HSJ1a and HSJ1b, in reducing polyglutamine-mediated protein inclusion formation.
  • To elucidate the molecular mechanisms by which HSJ1 proteins exert their effects on protein aggregation and degradation.
  • To evaluate the therapeutic potential of targeting the ubiquitin-proteasome system (UPS) for polyglutamine diseases.

Main Methods:

  • Expression of heat shock proteins (hsp70, hsp40, HSJ1a, HSJ1b) in cellular models of spinal and bulbar muscular atrophy (SBMA) and general protein aggregation.
  • Assessment of protein inclusion formation using microscopy.
  • Analysis of protein refolding and ubiquitylation levels.
  • Investigation of HSJ1a interaction with ubiquitylated proteins using a luciferase complex model.
  • Evaluation of HSJ1a expression in an in vivo model of polyglutamine disease.

Main Results:

  • Expression of hsp70, hsp40, HSJ1a, and HSJ1b significantly reduced protein inclusion formation in SBMA models.
  • HSJ1a significantly decreased inclusion formation in a primary neuronal model.
  • Hsp70 and hsp40 enhanced chaperone-mediated refolding, while HSJ1 proteins increased ubiquitylation.
  • HSJ1a promoted the degradation of target proteins via the ubiquitin-proteasome system (UPS).
  • HSJ1a expression reduced the number of neurons with inclusions in an in vivo polyglutamine disease model.

Conclusions:

  • HSJ1 proteins effectively reduce polyglutamine-mediated protein inclusions by promoting degradation through the UPS.
  • Targeting the UPS to enhance the clearance of misfolded proteins represents a promising therapeutic strategy for polyglutamine diseases.
  • HSJ1 proteins offer a potential therapeutic target for treating neurodegenerative conditions associated with protein aggregation.