Related Experiment Video

Updated: Jul 9, 2025

Study of the Functions and Activities of Neuronal K-Cl Co-Transporter KCC2 Using Western Blotting
10:08

Study of the Functions and Activities of Neuronal K-Cl Co-Transporter KCC2 Using Western Blotting

Published on: December 9, 2022

2.2K

Dephosphorylation of NFAT by Calcineurin inhibits Skp2-mediated degradation

Shunsuke Hanaki1, Makoto Habara1, Yuki Sato1

  • 1Department of Veterinary Biochemistry, Yamaguchi University, 1677-1 Yoshida, Yamaguchi, Yamaguchi, 753-8511, Japan.

Journal of Biochemistry
|November 29, 2023
PubMed

Insights

Calcineurin dephosphorylation stabilizes Nuclear Factor of Activated T-cells (NFAT) by preventing its degradation. This process involves preventing Skp2-mediated degradation, highlighting a new role for calcineurin in NFAT protein stability.

Area of Science:

  • Molecular Biology
  • Cellular Biology
  • Immunology

Background:

  • Nuclear Factor of Activated T-cells (NFAT) is crucial for immune responses, development, and cancer.
  • Calcineurin, a phosphatase, activates NFAT via dephosphorylation upon calcium influx.
  • Mechanisms regulating NFAT protein degradation remain largely unknown.

Purpose of the Study:

  • To investigate the role of calcineurin in NFAT protein stability.
  • To determine if calcineurin influences NFAT degradation pathways.

Main Methods:

  • Utilized calcineurin inhibition and mutants to assess NFAT stability.
  • Manipulated intracellular calcium levels to observe NFAT stabilization.
  • Employed biochemical assays to identify proteins involved in NFAT degradation.

Main Results:

  • Calcineurin-mediated dephosphorylation of NFAT promotes its stabilization.
  • A calcineurin mutant lacking phosphatase activity failed to stabilize NFAT.
  • Increased intracellular calcium enhanced NFAT stability.
  • Identified S-phase kinase associated protein 2 (Skp2) as a mediator of NFAT degradation in the absence of calcineurin.

Conclusions:

  • Calcineurin dephosphorylation protects NFAT from Skp2-mediated degradation.
  • Calcineurin plays a critical role in stabilizing NFAT protein levels.
Keywords:
NFATSkp2calcineurincalciumphosphorylation

More Related Videos

A Guide to Production, Crystallization, and Structure Determination of Human IKK1/α11:27

A Guide to Production, Crystallization, and Structure Determination of Human IKK1/α

Published on: November 2, 2018

9.2K
Molecular Modulation by Lentivirus-Delivered Specific shRNAs in Endoplasmic Reticulum Stressed Neurons10:50

Molecular Modulation by Lentivirus-Delivered Specific shRNAs in Endoplasmic Reticulum Stressed Neurons

Published on: April 24, 2021

1.0K

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...
8.9K
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...
7.4K
Calmodulin-dependent Signaling01:16

Calmodulin-dependent Signaling

Calmodulin (CaM) is a calcium-binding protein in eukaryotes that controls various calcium-regulated cellular processes. It has four calcium-binding sites that bind calcium to form the calcium-calmodulin ( Ca2+-CaM) complex. GPCR stimulation increases the calcium levels in the cells that bind to CaM and induces a conformational change.
The Ca2+-CaM complex does not have enzymatic activity by itself. Instead, the complex binds downstream target proteins, including membrane proteins or enzymes,...
5.1K
Regulation of Nuclear Protein Sorting01:45

Regulation of Nuclear Protein Sorting

Nuclear protein sorting regulates nucleus composition and gene expression, crucial for determining the fate of a eukaryotic cell. Hence, the entry and exit of molecules across the nuclear envelope is a tightly controlled process. Nuclear protein sorting can be inhibited by one of the following ways: 1) masking cargo signal sequences, 2) modifying the nuclear receptor's affinity for cargo, 3) controlling the nuclear pore size, 4) retaining the cargo during its transit to the cytosol or the...
2.4K
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...
3.6K
Anaphase Promoting Complex00:50

Anaphase Promoting Complex

The stepwise destruction of specific proteins is necessary for the progression and completion of the cell cycle. Such proteins are ubiquitinated by ubiquitin ligases and then subsequently destroyed by the proteasome. The SCF (Skp1/Cullin/F-box) and the anaphase-promoting complex (APC) are two important ubiquitin ligases involved in cell cycle progression. While SCF is active throughout the cell cycle, APC gets activated during metaphase to anaphase transition. Cdc20 or Cdh1 binds to APC and...
2.9K