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

NF-κB-dependent Signaling Pathway02:26

NF-κB-dependent Signaling Pathway

The transcription factor NF-κB was discovered in 1986 in the lab of Nobel laureate Professor David Baltimore, for its interaction with the immunoglobulin light chain enhancer in B-cells. After more than three decades of study, it is now evident that NF-κB regulates the expression of over 100 genes. Most of these genes play an essential role in the innate and adaptive immune responses as well as the inflammatory responses of animals.
NF-κB-dependent Signaling Mechanism
The heterodimer of NF-κB...
Drugs for Treatment of Crohn's Disease in IBD Using Biologic Agents: Anti-TNF01:24

Drugs for Treatment of Crohn's Disease in IBD Using Biologic Agents: Anti-TNF

Tumor Necrosis Factor (TNF), a proinflammatory cytokine, contributes significantly to the inflammation seen in Crohn's disease. It exists as soluble TNF and membrane-bound TNF, with actions mediated through TNF receptors (TNFR). TNFR activation leads to the release of proinflammatory cytokines, T-cell activation, collagen production, and leukocyte migration, all contributing to inflammation in Crohn's disease. Anti-TNF monoclonal antibodies, namely infliximab (Remicade), adalimumab (Humira),...
The JAK-STAT Signaling Pathway01:20

The JAK-STAT Signaling Pathway

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...
Caspases01:24

Caspases

Caspase, a family of cysteine proteases, serve as effectors in apoptosis. The ced3 gene in C.elegans was first identified to be involved in apoptosis. This gene encodes the ced-3 caspase that is similar to the interleukin-1-beta converting enzyme or ICE in mammals. In addition to apoptosis, caspases also function in the inflammatory response. Inflammatory caspases are essential in activating pro-inflammatory cytokines that recruit immune cells and block the replication of pathogens inside cells.
NF-kB-dependent Signaling Pathway02:26

NF-kB-dependent Signaling Pathway

The transcription factor NF-κB was discovered in 1986 in the lab of Nobel laureate Professor David Baltimore, for its interaction with the immunoglobulin light chain enhancer in B-cells. After more than three decades of study, it is now evident that NF-κB regulates the expression of over 100 genes. Most of these genes play an essential role in the innate and adaptive immune responses as well as the inflammatory responses of animals.
NF-κB-dependent Signaling Mechanism
The heterodimer of NF-κB...
The Extrinsic Apoptotic Pathway01:17

The Extrinsic Apoptotic Pathway

The extrinsic apoptotic pathway is initiated when extracellular death-inducing signals, such as specific cytokines, activate the death receptors expressed on the cell surface. The immune cells involved in this pathway are natural killer cells (NK cells) and cytotoxic T-lymphocytes. NK cells are critical in innate immune response, while cytotoxic T-lymphocytes are associated with adaptive immune response. These cells recognize specific receptors expressed on the altered cells and activate...

You might also read

Related Articles

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

Sort by
Same author

Standardized direct oral anticoagulants prescription for treatment of acute venous thromboembolism in the emergency department: A quality improvement initiative.

Thrombosis research·2024
Same author

Risk factors for TB in Australia and their association with delayed treatment completion.

The international journal of tuberculosis and lung disease : the official journal of the International Union against Tuberculosis and Lung Disease·2022
Same author

Management of anticoagulation in pregnant women with venous thromboembolism: An international survey of clinical practice.

Thrombosis research·2021
Same author

Porcine dermal collagen mesh (Permacol™) as a bioprosthesis in the ligation of intersphincteric tract (BioLIFT) procedure.

Techniques in coloproctology·2020
Same author

Corrigendum to "Delayed time to emergency hip surgery in patients taking oral anticoagulants" [Thromb Res. 184 (2019 Dec) 110-114].

Thrombosis research·2019
Same author

The impact of Recovery Colleges on mental health staff, services and society.

Epidemiology and psychiatric sciences·2018
Same journal

Chemotactic self-organization captures the dynamics of mammalian hair follicle patterning.

Proceedings of the National Academy of Sciences of the United States of America·2026
Same journal

Tomographic imaging of superconducting order using particle-hole interference.

Proceedings of the National Academy of Sciences of the United States of America·2026
Same journal

Inhibitory potential of autologous neutralizing antibodies sets quantitative limits on the rebound-competent HIV-1 reservoir.

Proceedings of the National Academy of Sciences of the United States of America·2026
Same journal

Inferring epidemiological parameters under an infectious phylogeography model with visitor dynamics.

Proceedings of the National Academy of Sciences of the United States of America·2026
Same journal

Analytical modeling for suction cup designs for skin-interfaced wearable devices.

Proceedings of the National Academy of Sciences of the United States of America·2026
Same journal

Improving cell-free metabolism through direct integration of artificial respiratory chains.

Proceedings of the National Academy of Sciences of the United States of America·2026
See all related articles

Related Experiment Video

Updated: Jul 2, 2026

A Guide to Production, Crystallization, and Structure Determination of Human IKK1/α
11:27

A Guide to Production, Crystallization, and Structure Determination of Human IKK1/α

Published on: November 2, 2018

Both cIAP1 and cIAP2 regulate TNFalpha-mediated NF-kappaB activation.

D J Mahoney1, H H Cheung, R Lejmi Mrad

  • 1Apoptosis Research Centre, Children's Hospital of Eastern Ontario, Ottawa, ON, Canada K1H 8L1.

Proceedings of the National Academy of Sciences of the United States of America
|August 14, 2008
PubMed
Summary
This summary is machine-generated.

Cellular inhibitor of apoptosis proteins 1 and 2 (cIAP1 and cIAP2) are crucial, redundant regulators of NF-kappaB activation by TNFalpha. Their combined absence sensitizes cells to TNFalpha-induced apoptosis.

More Related Videos

Myeloid Innate Signaling Pathway Regulation by MALT1 Paracaspase Activity
07:09

Myeloid Innate Signaling Pathway Regulation by MALT1 Paracaspase Activity

Published on: January 7, 2019

Mechanistic Insight into the Development of TNBS-Mediated Intestinal Fibrosis and Evaluating the Inhibitory Effects of Rapamycin
10:21

Mechanistic Insight into the Development of TNBS-Mediated Intestinal Fibrosis and Evaluating the Inhibitory Effects of Rapamycin

Published on: September 12, 2019

Related Experiment Videos

Last Updated: Jul 2, 2026

A Guide to Production, Crystallization, and Structure Determination of Human IKK1/α
11:27

A Guide to Production, Crystallization, and Structure Determination of Human IKK1/α

Published on: November 2, 2018

Myeloid Innate Signaling Pathway Regulation by MALT1 Paracaspase Activity
07:09

Myeloid Innate Signaling Pathway Regulation by MALT1 Paracaspase Activity

Published on: January 7, 2019

Mechanistic Insight into the Development of TNBS-Mediated Intestinal Fibrosis and Evaluating the Inhibitory Effects of Rapamycin
10:21

Mechanistic Insight into the Development of TNBS-Mediated Intestinal Fibrosis and Evaluating the Inhibitory Effects of Rapamycin

Published on: September 12, 2019

Area of Science:

  • Cellular and Molecular Biology
  • Immunology
  • Signal Transduction

Background:

  • Cellular inhibitor of apoptosis proteins 1 and 2 (cIAP1 and cIAP2) are implicated in NF-kappaB activation.
  • Previous studies suggested functional redundancy, as single gene deletions did not reveal a clear role.

Purpose of the Study:

  • To investigate the critical and redundant roles of cIAP1 and cIAP2 in NF-kappaB activation by TNFalpha.
  • To elucidate the mechanism by which cIAP1 and cIAP2 regulate TNFalpha-induced signaling.

Main Methods:

  • Combined genetic deletion and siRNA knockdown of cIAP1 and cIAP2.
  • Analysis of NF-kappaB activation, TNF receptor 1 (TNFR1) complex formation, and protein polyubiquitination.
  • Assessment of apoptosis in response to TNFalpha treatment.

Main Results:

  • Combined deficiency of cIAP1 and cIAP2, but not single deficiencies, severely blunted NF-kappaB activation by TNFalpha.
  • cIAP1 and cIAP2 were recruited to TNFR1 and were essential for the formation of a functional TNFR1 signalosome.
  • The polyubiquitination of receptor-interacting protein 1 (Rip1) was attenuated in cells lacking both cIAP1 and cIAP2.
  • This led to diminished inhibitor of kappaB kinase beta (IKKbeta) phosphorylation and blunted downstream signaling.
  • Cells lacking both cIAP1 and cIAP2 exhibited increased sensitivity to TNFalpha-mediated apoptosis.

Conclusions:

  • cIAP1 and cIAP2 are critical, redundant regulators of NF-kappaB activation downstream of TNFalpha.
  • Either cIAP1 or cIAP2 is required for Rip1 polyubiquitination and subsequent NF-kappaB signaling.
  • The dual loss of cIAP1 and cIAP2 compromises TNFR1 signalosome integrity, leading to apoptosis sensitization.