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 Experiment Videos

NF-kappaB activation: Nondegradative ubiquitination implicates NEMO.

Alain Israël1

  • 1Unité de Signalisation Moléculaire et Activation Cellulaire, URA 2582 CNRS Institut Pasteur, 75015 Paris, France. aisrael@pasteur.fr

Trends in Immunology
|July 22, 2006
PubMed
Summary

Non-degradative ubiquitination activates the IkappaB kinase (IKK) complex, crucial for nuclear factor (NF)-kappaB signaling. NEMO-IKKgamma specifically recognizes Lys63 ubiquitin chains on RIP1 kinase, which is essential for IKK activation after tumor necrosis factor treatment.

Related Concept Videos

You might also read

Related Articles

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

Sort by
Same author

Author Correction: TNF-mediated inflammatory skin disease in mice with epidermis-specific deletion of IKK2.

Nature·2025
Same author

Two NEMO-like Ubiquitin-Binding Domains in CEP55 Differently Regulate Cytokinesis.

iScience·2019
Same author

Super-resolution microscopy reveals a preformed NEMO lattice structure that is collapsed in incontinentia pigmenti.

Nature communications·2016
Same author

Erratum to: Flt3 receptor inhibition reduces constitutive NFκB activation in high-risk myelodysplastic syndrome and acute myeloid leukemia.

Apoptosis : an international journal on programmed cell death·2015
Same author

Human HOIP and LUBAC deficiency underlies autoinflammation, immunodeficiency, amylopectinosis, and lymphangiectasia.

The Journal of experimental medicine·2015
Same author

Phenotypic complementation of genetic immunodeficiency by chronic herpesvirus infection.

eLife·2015

Area of Science:

  • Molecular Biology
  • Cell Signaling
  • Immunology

Background:

  • Non-degradative ubiquitination plays a key role in cellular signaling pathways.
  • The IkappaB kinase (IKK) complex is central to the nuclear factor (NF)-kappaB signaling cascade.
  • Tumor necrosis factor (TNF) treatment initiates signaling cascades involving protein modifications.

Purpose of the Study:

  • To elucidate the specific molecular mechanisms by which non-degradative ubiquitination activates the IKK complex.
  • To identify the components involved in recognizing ubiquitination events within the NF-kappaB pathway.
  • To determine the role of Lys63 polyubiquitin chains in IKK activation.

Main Methods:

  • Investigating protein-protein interactions in the NF-kappaB signaling pathway.

Related Experiment Videos

  • Analyzing the role of ubiquitination in kinase complex activation.
  • Utilizing biochemical assays to study the recognition of polyubiquitin chains by IKK components.

    • Main Results:

    • NF-kappaB essential modulator (NEMO)-IKKgamma specifically recognizes Lys63 polyubiquitin chains.
    • These chains are attached to the receptor-interacting protein (RIP)1 kinase.
    • Recognition of these ubiquitin chains by NEMO-IKKgamma is a prerequisite for IKK complex activation following TNF treatment.

    Conclusions:

    • Non-degradative ubiquitination, specifically Lys63 polyubiquitination of RIP1 kinase, is a critical signal for IKK activation.
    • NEMO-IKKgamma acts as a sensor for these specific ubiquitin chains, linking ubiquitination events to NF-kappaB pathway activation.
    • These findings provide a detailed molecular understanding of how ubiquitination regulates a key inflammatory signaling cascade.