Related Experiment Video

Updated: Apr 18, 2026

Measuring Composition of CD95 Death-Inducing Signaling Complex and Processing of Procaspase-8 in this Complex
07:17

Measuring Composition of CD95 Death-Inducing Signaling Complex and Processing of Procaspase-8 in this Complex

Published on: August 2, 2021

3.1K

A RIPK3-caspase 8 complex mediates atypical pro-IL-1β processing

Kenta Moriwaki1, John Bertin2, Peter J Gough2

  • 1Department of Pathology, Program in Immunology & Microbiology, University of Massachusetts Medical School, Worcester, MA 01655; and.

Journal of Immunology (Baltimore, Md. : 1950)
|January 9, 2015
PubMed

Insights

Receptor interacting protein kinase 3 (RIPK3) unexpectedly promotes caspase 8 activation, enhancing interleukin-1 beta (IL-1β) maturation in dendritic cells. This finding clarifies RIPK3

Area of Science:

  • Immunology
  • Cellular signaling
  • Inflammation

Background:

  • Caspase 8 regulates apoptosis and necroptosis, and its role in IL-1β processing is complex.
  • Receptor interacting protein kinase 3 (RIPK3) is known to mediate necroptosis but its interaction with caspase 8 in IL-1β processing is unclear.

Purpose of the Study:

  • To elucidate the biochemical complex and mechanism underlying caspase 8-mediated pro-IL-1β processing.
  • To investigate the role of RIPK3 in caspase 8 activation and IL-1β maturation in response to LPS.

Main Methods:

  • Experiments were conducted using bone marrow-derived dendritic cells (BMDCs) stimulated with LPS.
  • Analysis involved assessing caspase 8 activation, pro-IL-1β processing, and protein complex formation.
  • Studies utilized RIPK3-specific kinase inhibitors and kinase-inactive RIPK1/RIPK3 mutants.

Main Results:

  • RIPK3 is essential for both caspase 1- and caspase 8-mediated pro-IL-1β and pro-IL-18 processing in LPS-stimulated BMDCs.
  • Caspase 8-mediated pro-IL-1β processing requires RIPK1, RIPK3, TRIF, and FADD, forming a complex with caspase 8.
  • RIPK3 kinase inhibitors enhanced caspase 8 activation and IL-1β processing, while kinase activity of RIPK1/RIPK3 was not required for LPS-induced IL-1β secretion.

Conclusions:

  • RIPK3 acts as a positive regulator of caspase 8 activity, promoting IL-1β maturation in BMDCs.
  • The kinase activity of RIPK1 and RIPK3 is dispensable for LPS-induced caspase 8 activation and IL-1β secretion.

More Related Videos

Evaluation of Caspase Activation to Assess Innate Immune Cell Death10:23

Evaluation of Caspase Activation to Assess Innate Immune Cell Death

Published on: January 20, 2023

4.0K
Visualization of Inflammatory Caspases Induced Proximity in Human Monocyte-Derived Macrophages08:41

Visualization of Inflammatory Caspases Induced Proximity in Human Monocyte-Derived Macrophages

Published on: April 6, 2022

3.2K

Related Concept Videos

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...
14.7K
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...
9.5K
Regulation of the Unfolded Protein Response01:31

Regulation of the Unfolded Protein Response

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...
3.3K
The Intrinsic Apoptotic Pathway01:31

The Intrinsic Apoptotic Pathway

Internal cellular stress, such as cellular injury or hypoxia, triggers intrinsic apoptosis. The B-cell lymphoma 2 (Bcl-2) family of proteins are the primary regulators of the intrinsic apoptotic pathway. For example, during DNA damage, checkpoint proteins, such as Ataxia Telangiectasia Mutated (ATM protein) and Checkpoints Factor-2 (Chk2) proteins, are activated. These proteins phosphorylate p53 which further activates pro-apoptotic proteins, such as Bax, Bak, PUMA, and Noxa, and inhibits...
9.3K
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...
14.2K
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...
7.1K