Related Experiment Video
Updated: Feb 6, 2026
09:36
Recombinant α- β- and γ-Synucleins Stimulate Protein Phosphatase 2A Catalytic Subunit Activity in Cell Free Assays
Published on: August 13, 2017
7.1K
Pyruvate dehydrogenase phosphatase catalytic subunit 2 limits Th17 differentiation
Michihito Kono1, Nobuya Yoshida1, Kayaho Maeda2
1Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215 m-kono@hokudai.ac.jp nyoshida@bidmc.harvard.edu gtsokos@bidmc.harvard.edu.
Summary
The inducible cAMP early repressor/cAMP response element modulator (ICER/CREM) transcription factor directly controls Th17 cell metabolism. ICER/CREM regulates pyruvate dehydrogenase phosphatase 2 (PDP2) to influence energy production in Th17 differentiation and systemic lupus erythematosus (SLE).
Area of Science:
- Immunology
- Cell Metabolism
- Molecular Biology
Background:
- Th17 cells utilize glycolytic metabolism.
- Pyruvate dehydrogenase (PDH) is a key metabolic enzyme.
- The transcription factor ICER/CREM is implicated in Th17 cells and SLE.
Purpose of the Study:
- To investigate the role of ICER/CREM in regulating Th17 cell metabolism.
- To determine the effect of ICER/CREM on pyruvate dehydrogenase phosphatase 2 (PDP2) expression and activity.
- To explore the translational relevance in systemic lupus erythematosus (SLE).
Main Methods:
- In vitro Th17 cell polarization.
- Analysis of gene and protein expression (PDP2, PDH).
- ChIP assays to assess transcription factor binding.
- In vivo studies using knockout/knockdown models and mouse models of SLE.
- Analysis of patient samples.
Main Results:
- ICER/CREM deficiency increased glycolysis and lactate production in Th17 cells.
- ICER/CREM suppressed PDP2 expression by binding to its promoter.
- PDP2 suppressed Th17 differentiation, while its suppression enhanced it and worsened experimental autoimmune encephalomyelitis.
- PDP2 expression was decreased in SLE patients, and its forced expression suppressed Th17 differentiation in SLE models.
Conclusions:
- ICER/CREM directly controls energy metabolism at the PDH level during Th17 differentiation.
- The ICER/CREM-PDP2 axis is a critical regulator of Th17 cell function in health and SLE.
- Targeting this axis may offer therapeutic potential for SLE.
More Related Videos
Related Concept Videos
02:54Protein Kinases and Phosphatases
15.2K
Proteins undergo chemical modifications that trigger changes in the charge, structure, and conformation of the proteins. Phosphorylation, acetylation, glycosylation, nitrosylation, ubiquitination, lipidation, methylation, and proteolysis are various protein modifications that regulate protein activity. Such modifications are usually enzyme-driven.
Protein kinases
Many proteins in the cell are regulated by phosphorylation, the addition of a phosphate group. A family of enzymes called kinases...
Protein kinases
Many proteins in the cell are regulated by phosphorylation, the addition of a phosphate group. A family of enzymes called kinases...
15.2K
02:54Protein Kinases and Phosphatases
4.5K
4.5K
01:15Pyruvate Oxidation
169.0K
After glycolysis, the charged pyruvate molecules enter the mitochondria via active transport and undergo three enzymatic reactions. These reactions ensure that pyruvate can enter the next metabolic pathway so that energy stored in the pyruvate molecules can be harnessed by the cells.
First, the enzyme pyruvate dehydrogenase removes the carboxyl group from pyruvate and releases it as carbon dioxide. The stripped molecule is then oxidized and releases electrons, which are then picked up by NAD+...
First, the enzyme pyruvate dehydrogenase removes the carboxyl group from pyruvate and releases it as carbon dioxide. The stripped molecule is then oxidized and releases electrons, which are then picked up by NAD+...
169.0K
01:20Fates of Pyruvate
11.0K
Pyruvate is the end product of glycolysis, where glucose is oxidized to pyruvate, simultaneously reducing NAD+ to NADH. Two molecules of ATP are also produced by substrate-level phosphorylation.
In aerobic organisms, pyruvate is metabolized via the citric acid cycle to produce reduced coenzymes NADH and FADH2. These coenzymes are then oxidized in the electron transport chain to produce ATP and, in the process, regenerate the NAD+ and FAD. As seen in some cell types and organisms, fermentation...
In aerobic organisms, pyruvate is metabolized via the citric acid cycle to produce reduced coenzymes NADH and FADH2. These coenzymes are then oxidized in the electron transport chain to produce ATP and, in the process, regenerate the NAD+ and FAD. As seen in some cell types and organisms, fermentation...
11.0K
02:27Limiting Reactant
70.1K
The relative amounts of reactants and products represented in a balanced chemical equation are often referred to as stoichiometric amounts. However, in reality, the reactants are not always present in the stoichiometric amounts indicated by the balanced equation.
70.1K
01:19Turnover Number and Catalytic Efficiency
21.6K
The turnover number of an enzyme is the maximum number of substrate molecules it can transform per unit time. Turnover numbers for most enzymes range from 1 to 1000 molecules per second. Catalase has the known highest turnover number, capable of converting up to 2.8×106 molecules of hydrogen peroxide into water and oxygen per second. Lysozyme has the lowest known turnover number of half a molecule per second.
Chymotrypsin is a pancreatic enzyme that breaks down proteins during digestion....
Chymotrypsin is a pancreatic enzyme that breaks down proteins during digestion....
21.6K