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

Regulation of the Unfolded Protein Response01:31

Regulation of the Unfolded Protein Response

2.4K
Inositol-requiring kinase one or IRE1 is the most conserved eukaryotic unfolded protein response (UPR) receptor. It is a type I transmembrane protein kinase receptor with a distinctive site-specific RNase activity. As the binding mechanics of the misfolded proteins with the N-terminal domain of IRE-1 are unclear, three binding models — direct, indirect, and allosteric -- are proposed for receptor activation. Nevertheless, it is known that once a misfolded protein associates with IRE1, it...
2.4K
Cell Signaling Feedback Loops01:07

Cell Signaling Feedback Loops

6.2K
Positive and negative feedback loops are crucial for regulating biological signaling systems. These feedback loops are processes that connect output signals to their inputs.
Negative feedback loops
Most signaling systems have negative feedback loops that can perform different functions such as output limiter, and adaptation.
Output limiter
Upon receiving an input signal, the cellular response rapidly increases until a threshold is reached. Beyond this threshold, a negative feedback loop...
6.2K
The Unfolded Protein Response01:37

The Unfolded Protein Response

4.5K
The ER is the hub of protein synthesis in a cell. It has robust systems to quality control protein folding and also for degradation of terminally misfolded proteins. Under normal conditions, a small proportion of misfolded proteins that cannot be salvaged need to be transported to the cytoplasm by the ER-associated degradation or ERAD pathways. However, if the ERAD cannot handle the misfolded proteins, the cell activates the unfolded protein response or UPR to adjust the protein folding...
4.5K
Amplifying Signals via Enzymatic Cascade01:22

Amplifying Signals via Enzymatic Cascade

8.4K
When a ligand binds to a cell-surface receptor, the receptor's intracellular domain changes shape, which may either activate its enzyme function or allow its binding to other molecules. The initial signal is amplified by most signal transduction pathways. This means that a single ligand molecule can activate multiple molecules of a downstream target. Proteins that relay a signal are most commonly phosphorylated at one or more sites, activating or inactivating the protein. Kinases catalyze...
8.4K
The Proteasome01:13

The Proteasome

827
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...
827
The JAK-STAT Signaling Pathway01:20

The JAK-STAT Signaling Pathway

8.8K
Several cytokine receptors have tightly bound Janus kinase or JAK proteins attached at their cytosolic tail. Small signaling molecules such as cytokines, growth hormones, or prolactins bind to the cytokine receptors and initiate their dimerization. The dimerization brings the cytosolic JAKs together that trans-phosphorylate and activates each other. The activated JAKs now phosphorylate cytosolic tails of the cytokine receptors, which serve as binding sites for adaptor proteins such as  SH2...
8.8K

You might also read

Related Articles

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

Sort by
Same author

A β-carboline natural product induces oxidative stress in <i>Fusarium graminearum</i> and limits the virulence of multiple fungal phytopathogens.

mBio·2026
Same author

Developing a pan cancer therapy based on DISE-inducing short RNAs.

Molecular therapy. Nucleic acids·2026
Same author

Multi-omics analysis reveals LARP1 as a key integrator of translation and metabolism in AML.

Oncogenesis·2026
Same author

Dual E3 ligase recruitment by monovalent degraders for tunable SMARCA 2/4 degradation.

Nature chemical biology·2026
Same author

Transcriptomic analysis of Rnq1 loss and prionization reveals alterations in translation pathways and energy metabolism.

Scientific reports·2026
Same author

Heat shock transcription factors in development and disease.

Disease models & mechanisms·2026

Related Experiment Video

Updated: Jun 21, 2025

Measurements of Physiological Stress Responses in C. Elegans
10:36

Measurements of Physiological Stress Responses in C. Elegans

Published on: May 21, 2020

13.9K

An HSF1-JMJD6-HSP feedback circuit promotes cell adaptation to proteotoxic stress.

Milad J Alasady1,2,3, Martina Koeva4,5,6, Seesha R Takagishi1,2,3

  • 1Department of Biochemistry and Molecular Genetics, Northwestern University Feinberg School of Medicine, Chicago, IL 60611.

Proceedings of the National Academy of Sciences of the United States of America
|July 10, 2024
PubMed
Summary

Heat Shock Factor 1 (HSF1) activates Jumonji domain-containing protein 6 (JMJD6) expression. JMJD6 then enhances HSF1 activity, creating a feedback loop crucial for cellular adaptation to proteotoxic stress and maintaining protein homeostasis.

Keywords:
HSF1JMJD6proteostasis

More Related Videos

Intracellular Refolding Assay
07:18

Intracellular Refolding Assay

Published on: January 24, 2012

14.2K
Coupled Assays for Monitoring Protein Refolding in Saccharomyces cerevisiae
13:52

Coupled Assays for Monitoring Protein Refolding in Saccharomyces cerevisiae

Published on: July 9, 2013

10.3K

Related Experiment Videos

Last Updated: Jun 21, 2025

Measurements of Physiological Stress Responses in C. Elegans
10:36

Measurements of Physiological Stress Responses in C. Elegans

Published on: May 21, 2020

13.9K
Intracellular Refolding Assay
07:18

Intracellular Refolding Assay

Published on: January 24, 2012

14.2K
Coupled Assays for Monitoring Protein Refolding in Saccharomyces cerevisiae
13:52

Coupled Assays for Monitoring Protein Refolding in Saccharomyces cerevisiae

Published on: July 9, 2013

10.3K

Area of Science:

  • Molecular Biology
  • Cellular Stress Response

Background:

  • Heat Shock Factor 1 (HSF1) is the primary regulator of the heat-shock response (HSR).
  • The HSR is vital for maintaining protein homeostasis (proteostasis) under cellular stress.
  • Understanding HSF1 regulation is key to comprehending cellular adaptive mechanisms.

Purpose of the Study:

  • To identify novel mediators of HSF1 activity in the heat-shock response.
  • To elucidate the regulatory role of Jumonji domain-containing protein 6 (JMJD6) in proteostasis.
  • To characterize the feedback mechanism between HSF1 and JMJD6.

Main Methods:

  • Genome-wide RNA interference (RNAi) library screening.
  • Utilized a heat-shock response (HSR) reporter system.
  • Investigated protein-protein interactions and transcriptional regulation.

Main Results:

  • Identified JMJD6 as a critical mediator of HSF1 activity.
  • Demonstrated that JMJD6 is a transcriptional target of HSF1, forming a positive feedback loop.
  • Showed that JMJD6 modulates HSP70 monomethylation, disrupting repressive complexes and enhancing HSF1 activation.

Conclusions:

  • JMJD6 is intricately integrated into the proteostasis network.
  • JMJD6 plays a crucial role in cellular adaptation to proteotoxic stress.
  • The HSF1-JMJD6 feedback circuit is essential for robust proteostasis maintenance.