Related Experiment Video

Updated: Aug 1, 2026

Identification of Mediators of T-cell Receptor Signaling via the Screening of Chemical Inhibitor Libraries
08:49

Identification of Mediators of T-cell Receptor Signaling via the Screening of Chemical Inhibitor Libraries

Published on: January 22, 2019

Characterization of a gene encoding two isoforms of a mitochondrial protein up-regulated by cyclosporin A in

Laurent Mascarell1, Rodolphe Auger, Andres Alcover

  • 1Unité de Biologie des Populations Lymphocytaires, CNRS 2582, Institut Pasteur, Paris, France.

The Journal of Biological Chemistry
|December 20, 2003
PubMed

Insights

Cyclosporin A (CSA) up-regulates a new gene, CSTAD, in T cells. Its protein products target mitochondria, altering membrane potential without causing cell death, revealing a novel CSA mechanism.

Area of Science:

  • Immunology
  • Molecular Biology
  • Cell Biology

Background:

  • Cyclosporin A (CSA) is a crucial immunosuppressor in organ transplantation.
  • CSA treatment of T cells induces the synthesis of numerous novel proteins.
  • Understanding these CSA-induced proteins offers insights into immunosuppressive mechanisms.

Purpose of the Study:

  • To identify and characterize genes induced by CSA during T cell activation.
  • To elucidate the function and cellular localization of the encoded proteins.
  • To reveal a novel mechanism of action for Cyclosporin A.

Main Methods:

  • Representational difference analysis and cDNA bank screening to identify induced genes.
  • Analysis of gene expression in response to CSA, FK506, and rapamycin.
  • In vivo studies in mice immunized with CSA.
  • Microscopic and cytofluorimetric analysis of protein localization and mitochondrial function.

Main Results:

  • Identified and cloned the CSA-conditional, T cell activation-dependent (CSTAD) gene.
  • CSTAD produces two protein isoforms (CSTADp-S and CSTADp-L) via alternative splicing.
  • CSTAD gene expression is regulated by the calcineurin pathway, sensitive to CSA and FK506 but not rapamycin.
  • CSTAD proteins localize to the outer mitochondrial membrane, depolarize mitochondrial potential, but do not trigger apoptosis or necrosis.

Conclusions:

  • CSA up-regulates the CSTAD gene, encoding mitochondrial proteins.
  • CSTAD proteins modulate mitochondrial membrane potential, representing a novel CSA mechanism.
  • This discovery provides new avenues for understanding immunosuppression and T cell regulation.

More Related Videos

Generation of Orthotopic Pancreatic Tumors and Ex vivo Characterization of Tumor-Infiltrating T Cell Cytotoxicity06:16

Generation of Orthotopic Pancreatic Tumors and Ex vivo Characterization of Tumor-Infiltrating T Cell Cytotoxicity

Published on: December 7, 2019

Real-time Monitoring of Mitochondrial Respiration in Cytokine-differentiated Human Primary T Cells06:55

Real-time Monitoring of Mitochondrial Respiration in Cytokine-differentiated Human Primary T Cells

Published on: October 19, 2021

Related Concept Videos

Cell Specific Gene Expression01:58

Cell Specific Gene Expression

Multicellular organisms contain a variety of structurally and functionally distinct cell types, but the DNA in all the cells originated from the same parent cells. The differences in the cells can be attributed to the differential gene expression. Liver cells, whose functions include detoxification of blood, production of bile to metabolize fats, and synthesis of proteins essential for metabolism, must express a specific set of genes to perform their functions. Gene expression also varies with...
Master Transcription Regulators02:23

Master Transcription Regulators

Master transcription regulators are regulatory proteins that are predominantly responsible for regulating the expression of multiple genes. Often these genes work in concert to drive a  complex process. Activation of a master transcription regulator can lead to a cascade of transcriptional activation necessary for that outcome. These regulators can directly bind to the regulatory sequences of the various genes involved, or they can indirectly regulate transcription by binding to regulatory...
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...
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...
T Cell Activation and Clonal Selection01:22

T Cell Activation and Clonal Selection

T cells are integral to our adaptive immune system, recognizing and effectively responding to foreign antigens. T cell activation and clonal selection are pivotal in orchestrating this immune response. This article elucidates these mechanisms, detailing the roles of cluster of differentiation (CD) markers, major histocompatibility complex (MHC) molecules, costimulatory signals, and the process of clonal selection.
Naive T cells that have not yet encountered an antigen express two primary CD...
B Cell Activation and Differentiation01:24

B Cell Activation and Differentiation

The adaptive immune response, a sophisticated defense mechanism, relies on the activation and differentiation of B lymphocytes, or B cells. These processes enable our bodies to mount a tailored response against specific pathogens such as bacteria, free virus particles, toxins, and parasites.
When naive B cells encounter a specific antigen that can bind to the B cell receptor (BCR) on their surface, they undergo sensitization to respond to the antigen's presence. Sensitization begins with...