Related Experiment Video

Updated: May 24, 2026

Applying an Inducible Expression System to Study Interference of Bacterial Virulence Factors with Intracellular Signaling
08:51

Applying an Inducible Expression System to Study Interference of Bacterial Virulence Factors with Intracellular Signaling

Published on: June 25, 2015

ECRG4 is a negative regulator of caspase-8-mediated apoptosis in human T-leukemia cells

Junichi Matsuzaki1, Toshihiko Torigoe, Yoshihiko Hirohashi

  • 1Department of Pathology, Sapporo Medical University School of Medicine, South-1 West-17, Chuo-ku, Sapporo 060-8556, Japan.

Carcinogenesis
|March 14, 2012
PubMed

Insights

Esophageal cancer-related gene 4 (ECRG4) acts as an antiapoptotic factor in T cells. Overexpressing ECRG4 inhibits Fas-mediated apoptosis by interacting with caspase-8, suggesting a novel regulatory role.

Area of Science:

  • Cell Biology
  • Immunology
  • Molecular Biology

Background:

  • Fas-mediated apoptosis is crucial for T-cell homeostasis and immune regulation.
  • Dysregulation of apoptosis contributes to T-cell leukemia.
  • Previous studies identified aberrant gene expression in Fas-resistant T-cell lines.

Purpose of the Study:

  • To investigate the subcellular localization and function of esophageal cancer-related gene 4 (ECRG4) in Fas-mediated apoptosis.
  • To elucidate the molecular mechanisms by which ECRG4 influences apoptotic signaling pathways.
  • To determine the role of ECRG4 in T-cell survival and apoptosis.

Main Methods:

  • Confocal fluorescence microscopy to determine ECRG4 subcellular localization.
  • Gene transfection and overexpression studies in Jurkat and HeLa cell lines.
  • Mitochondrial membrane permeability assays.
  • Immunoprecipitation assays to identify protein interactions.
  • Caspase activity and substrate cleavage assays.

Main Results:

  • ECRG4 localizes to mitochondria, endoplasmic reticulum, and Golgi apparatus.
  • Overexpression of ECRG4 confers resistance to Fas- and TNF-alpha-induced apoptosis.
  • ECRG4 inhibits mitochondrial membrane permeability transition.
  • ECRG4 associates with procaspase-8, inhibiting its activity and Bid cleavage.
  • ECRG4 expression is downregulated in activated T cells.

Conclusions:

  • ECRG4 is a novel antiapoptotic gene involved in the negative regulation of caspase-8-mediated apoptosis in T cells.
  • ECRG4's interaction with procaspase-8 provides a mechanism for inhibiting apoptosis.
  • Downregulation of ECRG4 in activated T cells may contribute to their apoptotic sensitivity.

More Related Videos

Evaluation of Caspase Activation to Assess Innate Immune Cell Death10:23

Evaluation of Caspase Activation to Assess Innate Immune Cell Death

Published on: January 20, 2023

Measuring Caspase Activity Using a Fluorometric Assay or Flow Cytometry05:29

Measuring Caspase Activity Using a Fluorometric Assay or Flow Cytometry

Published on: March 24, 2023

Related Concept Videos

Caspases01:24

Caspases

Caspase, a family of cysteine proteases, serve as effectors in apoptosis. The ced3 gene in C.elegans was first identified to be involved in apoptosis. This gene encodes the ced-3 caspase that is similar to the interleukin-1-beta converting enzyme or ICE in mammals. In addition to apoptosis, caspases also function in the inflammatory response. Inflammatory caspases are essential in activating pro-inflammatory cytokines that recruit immune cells and block the replication of pathogens inside cells.
The Extrinsic Apoptotic Pathway01:17

The Extrinsic Apoptotic Pathway

The extrinsic apoptotic pathway is initiated when extracellular death-inducing signals, such as specific cytokines, activate the death receptors expressed on the cell surface. The immune cells involved in this pathway are natural killer cells (NK cells) and cytotoxic T-lymphocytes. NK cells are critical in innate immune response, while cytotoxic T-lymphocytes are associated with adaptive immune response. These cells recognize specific receptors expressed on the altered cells and activate...
Negative Regulator Molecules01:23

Negative Regulator Molecules

Positive regulators allow a cell to advance through cell cycle checkpoints. Negative regulators have an equally important role as they terminate a cell’s progression through the cell cycle—or pause it—until the cell meets specific criteria.
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...
Receptor Downregulation in MVBs01:15

Receptor Downregulation in MVBs

Multivesicular bodies (MVBs) are mature endosomes that sort ubiquitinated proteins and then fuse with lysosomes to degrade the sorted proteins. Epidermal growth factor (EGF) and its receptor (EGFR) form a complex that can be internalized through endocytosis, sorted into an MVB, and later degraded.
The EGFR can initiate signaling pathways that  lead to cell proliferation, migration, and differentiation. Overexpression of EGFR  stimulates cells to proliferate. Excessive  EGFR activation may...