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

Protein Complexes with Interchangeable Parts01:57

Protein Complexes with Interchangeable Parts

Groups of proteins may form a complex where each protein in this complex has a different role in the overall execution of the complex’s function. Often some of the proteins in the complex can be replaced by a closely related variant to give a complex that contains many of the same components yet is functionally distinct.
The SCF ubiquitin ligase is a protein complex of five individual proteins. This complex attaches ubiquitin to other target proteins to mark them for degradation. In order to...
Receptor Downregulation in MVBs01:15

Receptor Downregulation in MVBs

Multivesicular bodies (MVBs) are mature endosomes that sort ubiquitinated proteins and then fuse with lysosomes to degrade the sorted proteins. Epidermal growth factor (EGF) and its receptor (EGFR) form a complex that can be internalized through endocytosis, sorted into an MVB, and later degraded.
The EGFR can initiate signaling pathways that  lead to cell proliferation, migration, and differentiation. Overexpression of EGFR  stimulates cells to proliferate. Excessive  EGFR activation may...
Restarting Stalled Replication Forks02:37

Restarting Stalled Replication Forks

DNA replication is initiated at sites containing predefined DNA sequences known as origins of replication. DNA is unwound at these sites by the minichromosome maintenance (MCM) helicase and other factors such as Cdc45 and the associated GINS complex.The unwound single strands are protected by replication protein A (RPA) until DNA polymerase starts synthesizing DNA at the 5’ end of the strand in the same direction as the replication fork. To prevent the replication fork from falling apart, a...
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...
The Unfolded Protein Response01:37

The Unfolded Protein Response

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...
Long-patch Base Excision Repair01:02

Long-patch Base Excision Repair

Since the discovery of the two BER pathways, there has been a debate about how a cell chooses one pathway over the other and the factors determining this selection. Numerous in vitro experiments have pointed out multiple determinants for the sub-pathway selection. These are:

You might also read

Related Articles

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

Sort by
Same author

Potential role of tirabrutinib as part of an optimal treatment strategy for lymphomatosis cerebri: illustrative case.

Journal of neurosurgery. Case lessons·2026
Same author

Basement membrane turnover drivesfilopodial protease-independent invasion.

Journal of the Royal Society, Interface·2026
Same author

The atypical E3 ligase HOIL-1 safeguards the ribosome during cellular stress.

Nature cell biology·2026
Same author

Goals and trends in space exploration: An overview of the panel on exploration sessions at the committee on space research general assembly 2024.

Life sciences in space research·2026
Same author

Inhibition of PTCH1 drug efflux activity enhances chemotherapy efficacy against triple negative breast cancers.

Translational oncology·2026
Same author

Asymmetry in ubiquitin binding by A20 reveals early recognition features of the ubiquitin code.

FEBS letters·2026

Related Experiment Video

Updated: Jul 9, 2026

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

Fbx8 makes Arf6 refractory to function via ubiquitination.

Hajime Yano1, Itaru Kobayashi, Yasuhito Onodera

  • 1Department of Molecular Biology, Osaka Bioscience Institute, Osaka 565-0874, Japan.

Molecular Biology of the Cell
|December 21, 2007
PubMed
Summary

Fbx8 protein controls Arf6 activity, a key factor in tumor invasion. Loss of Fbx8 in breast cancer cells enhances Arf6 and promotes invasion, suggesting Fbx8 as a potential therapeutic target.

More Related Videos

In-vitro Reconstitution of Bacterial Ubiquitination and VCP/p97-mediated Elimination
07:58

In-vitro Reconstitution of Bacterial Ubiquitination and VCP/p97-mediated Elimination

Published on: January 2, 2026

Assaying Proteasomal Degradation in a Cell-free System in Plants
07:43

Assaying Proteasomal Degradation in a Cell-free System in Plants

Published on: March 26, 2014

Related Experiment Videos

Last Updated: Jul 9, 2026

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

In-vitro Reconstitution of Bacterial Ubiquitination and VCP/p97-mediated Elimination
07:58

In-vitro Reconstitution of Bacterial Ubiquitination and VCP/p97-mediated Elimination

Published on: January 2, 2026

Assaying Proteasomal Degradation in a Cell-free System in Plants
07:43

Assaying Proteasomal Degradation in a Cell-free System in Plants

Published on: March 26, 2014

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Cancer Research

Background:

  • The small GTP-binding protein Arf6 is vital for cellular functions, including tumor invasion, by regulating membrane remodeling.
  • Understanding the regulation of Arf6 is crucial for developing strategies against cancer metastasis.

Purpose of the Study:

  • To investigate the role of Fbx8, an F-box protein, in the regulation of Arf6.
  • To explore the potential involvement of Fbx8-Arf6 interaction in breast cancer invasion.

Main Methods:

  • Investigated the ubiquitination of Arf6 mediated by Fbx8.
  • Analyzed the effect of Fbx8 knockdown and forced expression on Arf6 activity and breast tumor cell invasion.
  • Examined the functional importance of Fbx8's F-box and Sec7 domains.

Main Results:

  • Fbx8 mediates the ubiquitination of Arf6, independent of immediate proteasomal degradation.
  • Fbx8 knockdown leads to Arf6 hyperactivation.
  • Fbx8 expression is reduced in invasive breast tumor cell lines where Arf6 is critical.
  • Forced Fbx8 expression suppresses Arf6 activity and invasion in these cells, requiring both F-box and Sec7 domains.

Conclusions:

  • Fbx8 acts as a novel suppressor of Arf6 activity through noncanonical ubiquitination.
  • Dysfunctional Fbx8 expression may contribute to the invasiveness of certain breast cancer cells.
  • Fbx8 represents a potential therapeutic target for inhibiting breast cancer metastasis.