Related Experiment Video

Updated: Aug 25, 2025

Characterization of MLKL-mediated Plasma Membrane Rupture in Necroptosis
08:55

Characterization of MLKL-mediated Plasma Membrane Rupture in Necroptosis

Published on: August 7, 2018

10.9K

Mechanisms of TNF-independent RIPK3-mediated cell death

Bart Tummers1, Douglas R Green2

  • 1Centre for Inflammation Biology and Cancer Immunology, Department of Inflammation Biology, School of Immunology and Microbial Sciences, King's College London, London SE1 1UL, U.K.

The Biochemical Journal
|October 14, 2022
PubMed

Insights

Receptor-interacting serine/threonine protein kinase 3 (RIPK3) regulates TNF-independent apoptosis and necroptosis. RIPK3 is crucial for cell death signaling via Toll-like receptors (TLR) 3/4 and zDNA-binding protein 1 (ZBP1).

Area of Science:

  • Cellular biology
  • Molecular mechanisms of cell death

Background:

  • Apoptosis and necroptosis are critical cell death pathways involved in organismal biology and human diseases.
  • Tumor necrosis factor (TNF) is a known inducer of both apoptosis and necroptosis, with well-described mechanisms.
  • TNF-independent pathways also trigger these cell death forms, involving pattern recognition receptors like Toll-like receptor (TLR)-3 and -4, and zDNA-binding protein 1 (ZBP1).

Purpose of the Study:

  • To review the complex mechanisms governing TNF-independent cell death.
  • To elucidate the role of receptor-interacting serine/threonine protein kinase 3 (RIPK3) in these alternative cell death pathways.

Main Methods:

  • Review of existing literature on cell death signaling pathways.
  • Analysis of the molecular interactions and signaling cascades involved in TNF-independent apoptosis and necroptosis.

Main Results:

  • Receptor-interacting serine/threonine protein kinase 3 (RIPK3) is essential for cell death signaling in TNF-independent pathways.
  • While RIPK3 is required for TNF-induced necroptosis, it mediates both apoptosis and necroptosis when triggered by TLR3/4 and ZBP1.
  • These findings highlight distinct roles for RIPK3 depending on the upstream signaling trigger.

Conclusions:

  • RIPK3 plays a pivotal, context-dependent role in regulating both apoptosis and necroptosis.
  • Understanding RIPK3's function in TNF-independent cell death is crucial for comprehending various human diseases and developing targeted therapies.
Keywords:
RIPK3apoptosiscell deathimmunologyinflammationnecroptosis

More Related Videos

Tyramide Signal Amplification for the Immunofluorescent Staining of ZBP1-Dependent Phosphorylation of RIPK3 and MLKL After HSV-1 Infection in Human Cells09:15

Tyramide Signal Amplification for the Immunofluorescent Staining of ZBP1-Dependent Phosphorylation of RIPK3 and MLKL After HSV-1 Infection in Human Cells

Published on: October 20, 2022

2.3K
Neutrophil Lifespan Extension with CLON-G and an In Vitro Spontaneous Death Assay05:52

Neutrophil Lifespan Extension with CLON-G and an In Vitro Spontaneous Death Assay

Published on: May 12, 2023

1.5K

Related Concept Videos

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...
6.5K
Necrosis01:16

Necrosis

Necrosis is considered as an “accidental” or unexpected form of cell death that ends in cell lysis. The first noticeable mention of “necrosis” was in 1859 when Rudolf Virchow used this term to describe advanced tissue breakdown in his compilation titled “Cell Pathology”.
Morphological Manifestations of Necrosis
Necrotic cells show different types of morphological appearance depending on the type of tissue and infection. In coagulative necrosis, cells become...
4.7K
Overview of Cell Death01:30

Overview of Cell Death

Cell death is an essential process where the body gets rid of old or damaged cells. Cell proliferation and death need to be balanced, as an imbalance between the two may lead to cancer or autoimmune diseases.
Cell death was observed in the early 19th century, but there was no experimental evidence to prove it. In 1842, Carl Vogt first discovered cell death in a metamorphic toad; however, it was not termed ‘cell death.’ Scientists discovered different cell death pathways only in the...
7.5K
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...
7.8K
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...
6.7K
Cells of the Innate Immune Response01:28

Cells of the Innate Immune Response

The innate immune response is an immediate and non-specific response against pathogens, acting swiftly to prevent the spread of infections. The primary cells involved in this response are phagocytes and natural killer (NK) cells.
Phagocytes
Phagocytes police the peripheral tissues by removing cellular debris and responding to the invasion of foreign substances or pathogens. Many phagocytes attack and remove microorganisms even before lymphocytes detect them. The human body has two general...
2.0K