Related Experiment Video

Updated: Aug 13, 2025

Exploring the Arginine Methylome by Nuclear Magnetic Resonance Spectroscopy
07:02

Exploring the Arginine Methylome by Nuclear Magnetic Resonance Spectroscopy

Published on: December 16, 2021

1.5K

PRMT5-mediated regulatory arginine methylation of RIPK3

Chanchal Chauhan1, Ana Martinez-Val2, Rainer Niedenthal1

  • 1Institute of Cell Biochemistry, Hannover Medical School, Hannover, 30625, Germany.

Cell Death Discovery
|January 19, 2023
PubMed

Insights

Protein-arginine methyltransferase 5 (PRMT5) methylates RIPK3, a key regulator of cell death. This methylation acts as a feedback mechanism, controlling RIPK1 activity and influencing cell fate decisions in death signaling pathways.

Area of Science:

  • Cellular biology
  • Molecular signaling
  • Biochemistry

Background:

  • Tumor necrosis factor receptor-interacting protein kinases (RIPK) 1 and 3 regulate extrinsic cell death pathways.
  • RIPK1 controls cell survival or death decisions by forming distinct signaling complexes.
  • RIPK3 mediates necroptotic cell death.

Purpose of the Study:

  • To identify new components of the ripoptosome/necrosome complex.
  • To investigate the role of PRMT5 in RIPK1/RIPK3 signaling.
  • To elucidate the mechanism of PRMT5-mediated regulation of RIPK3.

Main Methods:

  • Mass spectrometry-based screening to identify protein interactions.
  • Biochemical assays to study protein methylation.
  • Site-directed mutagenesis to create non-methylatable RIPK3 variants.
  • Rescue experiments to validate functional significance.

Main Results:

  • PRMT5 was identified as a direct interaction partner of RIPK1.
  • RIPK3, but not RIPK1, was found to be a target of PRMT5-mediated symmetric arginine dimethylation at a conserved residue (R486 in human RIPK3).
  • Mutations abrogating RIPK3 methylation impaired its feedback control on RIPK1 activity.

Conclusions:

  • PRMT5-mediated RIPK3 methylation is a novel mechanism for feedback regulation in RIPK1-dependent signaling.
  • This post-translational modification fine-tunes RIPK1 activity and influences cell death decisions.
  • The study reveals a new layer of control in extrinsic cell death pathways.

More Related Videos

Quantitative Methods to Study Protein Arginine Methyltransferase 1-9 Activity in Cells08:11

Quantitative Methods to Study Protein Arginine Methyltransferase 1-9 Activity in Cells

Published on: August 7, 2021

4.2K
In vitro Methylation Assay to Study Protein Arginine Methylation10:01

In vitro Methylation Assay to Study Protein Arginine Methylation

Published on: October 5, 2014

15.4K

Related Concept Videos

PI3K/mTOR/AKT Signaling Pathway01:22

PI3K/mTOR/AKT Signaling Pathway

The mammalian target of rapamycin  (mTOR) is a serine/threonine kinase that regulates growth, proliferation, and cell survival in response to hormones, growth factors, or nutrient availability. This kinase exists in two structurally and functionally distinct forms: mTOR complex 1  (mTORC1) and mTOR complex 2  (mTORC2). The first form (mTORC1) is composed of a rapamycin-sensitive Raptor and proline-rich Akt substrate, PRAS40. In contrast,  mTORC2 consists of a...
3.8K
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...
2.5K
Protein Modifications in the RER01:26

Protein Modifications in the RER

Modification of secretory and transmembrane proteins entering the rough ER begins in the ER lumen. These modifications aid in protein folding and stabilize the acquired tertiary structure. Protein modifications in the rough ER co-occur at different stages of protein folding.
Broadly, these modifications can be categorized into four main categories — glycosylation, formation of disulfide bonds, assembly of protein subunits, and specific proteolytic cleavages like removal of signal...
5.4K
Riboswitches01:56

Riboswitches

Riboswitches are non-coding mRNA domains that regulate the transcription and translation of downstream genes without the help of proteins. Riboswitches bind directly to a metabolite and can form unique stem-loop or hairpin structures in response to the amount of the metabolite present. They have two distinct regions – a metabolite-binding aptamer and an expression platform.
The aptamer has high specificity for a particular metabolite which allows riboswitches to specifically regulate...
8.3K
MAPK Signaling Cascades01:07

MAPK Signaling Cascades

Mitogen-activated protein kinase, or MAPK pathway, activates three sequential kinases to regulate cellular responses such as proliferation, differentiation, survival, and apoptosis. The canonical MAPK pathway starts with a mitogen or growth factor binding to an RTK. The activated RTKs stimulate Ras, which recruits Raf or MAP3 Kinase (MAPKKK), the first kinase of the MAPK signaling cascade. Raf further phosphorylates and activates MEK or MAP2 Kinases (MAPKK), which in turn phosphorylates MAP...
5.8K
mTOR Signaling and Cancer Progression03:03

mTOR Signaling and Cancer Progression

The mammalian target of rapamycin or mTOR protein was discovered in 1994 due to its direct interaction with rapamycin. The protein gets its name from a yeast homolog called TOR. The mTOR protein complex in mammalian cells plays a major role in balancing anabolic processes such as the synthesis of proteins, lipids, and nucleotides and catabolic processes, such as autophagy in response to environmental cues, such as availability of nutrients and growth factors.
The mTOR pathway or the...
3.8K