Related Experiment Video

Updated: Jun 6, 2026

Native Polyacrylamide Gel Electrophoresis Immunoblot Analysis of Endogenous IRF5 Dimerization
08:57

Native Polyacrylamide Gel Electrophoresis Immunoblot Analysis of Endogenous IRF5 Dimerization

Published on: October 6, 2019

MDA5 is SUMOylated by PIAS2β in the upregulation of type I interferon signaling

Jihuan Fu1, Yanbao Xiong, Youli Xu

  • 1Key Laboratory of Infection and Immunity of Chinese Academy of Sciences, the Institute of Biophysics, 15 Da Tun Road, Chaoyang District, Beijing 100101, China.

Molecular Immunology
|December 16, 2010
PubMed

Insights

Melanoma differentiation-associated gene 5 (MDA5) SUMOylation enhances interferon production against viral infections. This modification, involving SUMO-1 and Ubc9, is crucial for the innate immune response.

Area of Science:

  • Immunology
  • Molecular Biology
  • Virology

Background:

  • Retinoic acid-inducible protein I (RIG-I) and melanoma differentiation-associated gene 5 (MDA5) are key cytosolic sensors of viral RNA.
  • These sensors initiate the type I interferon (IFN) production, a critical component of the innate immune response against viral pathogens.

Purpose of the Study:

  • To investigate the role of post-translational modifications, specifically SUMOylation, in MDA5-mediated antiviral signaling.
  • To elucidate the molecular mechanisms by which MDA5 SUMOylation impacts IFN production and viral replication.

Main Methods:

  • Stimulation of cells with polyI:C to mimic viral RNA presence.
  • Analysis of MDA5 SUMOylation levels using specific antibodies.
  • Overexpression and knockdown studies of SUMO-1, Ubc9, and PIAS2β.
  • Measurement of IFN expression and viral replication rates.

Main Results:

  • MDA5 undergoes inducible SUMOylation by SUMO-1 upon polyI:C stimulation.
  • Enhanced MDA5 SUMOylation by Ubc9 correlated with increased IFN expression and reduced viral replication.
  • PIAS2β, a SUMOylation E3 ligase, directly interacts with and enhances MDA5 SUMOylation.
  • Knockdown of Ubc9 or PIAS2β impaired MDA5 SUMOylation and subsequent IFN production.

Conclusions:

  • SUMO-1 modification of MDA5, potentially mediated by PIAS2β, plays a significant role in the MDA5-dependent IFN response to viral infections.
  • This SUMOylation process is a critical regulatory mechanism in innate immunity against viruses.

More Related Videos

A High Resolution Method to Monitor Phosphorylation-dependent Activation of IRF311:44

A High Resolution Method to Monitor Phosphorylation-dependent Activation of IRF3

Published on: January 24, 2016

Monitoring Activation of the Antiviral Pattern Recognition Receptors RIG-I And PKR By Limited Protease Digestion and Native PAGE12:43

Monitoring Activation of the Antiviral Pattern Recognition Receptors RIG-I And PKR By Limited Protease Digestion and Native PAGE

Published on: July 29, 2014

Related Concept Videos

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...
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 rapamycin-insensitive companion...
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...
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...
Abnormal Proliferation02:23

Abnormal Proliferation

Under normal conditions, most adult cells remain in a non-proliferative state unless stimulated by internal or external factors to replace lost cells. Abnormal cell proliferation is a condition in which the cell's growth exceeds and is uncoordinated with normal cells. In such situations, cell division persists in the same excessive manner even after cessation of the stimuli, leading to persistent tumors. The tumor arises from the damaged cells that replicate to pass the damage to the daughter...
Translocation of Proteins into the Mitochondria01:19

Translocation of Proteins into the Mitochondria

Mitochondrial precursors are translocated to the internal subcompartments via independent mechanisms involving distinct protein machineries called translocases.
Sorting of outer membrane proteins:
Mitochondrial outer membrane proteins are of two types: the transmembrane, beta-barrel porins, and the membrane-anchored, alpha-helical proteins. Beta-barrel porin precursors are translocated by the TOM complex and inserted into the outer mitochondrial membrane by the SAM complex. In contrast,...