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Updated: Aug 14, 2026

Development of an Antigen-driven Colitis Model to Study Presentation of Antigens by Antigen Presenting Cells to T Cells
06:57

Development of an Antigen-driven Colitis Model to Study Presentation of Antigens by Antigen Presenting Cells to T Cells

Published on: September 18, 2016

Serologically defined colon cancer antigen 3 is necessary for the presentation of TNF receptor 1 on cell surface

Nickolay Neznanov1, Lubov Neznanova, Brigitte Angres

  • 1Department of Molecular Genetics, Lerner Research Institute, Cleveland Clinic Foundation, OH 44195, USA. neznann@ccf.org

DNA and Cell Biology
|December 8, 2005
PubMed

Insights

Tumor necrosis factor (TNF) triggers cell death, but SDCCAG3 protein protects cells. Inhibiting SDCCAG3 reduces cell surface TNFR1, making cells resistant to TNF-induced apoptosis.

Area of Science:

  • Cellular biology
  • Molecular oncology
  • Immunology

Background:

  • Tumor necrosis factor (TNF) induces apoptosis in sensitive cells, especially when combined with transcription or translation inhibitors.
  • Identifying genetic factors that confer resistance to TNF-stimulated cell death is crucial for understanding cellular survival mechanisms.

Purpose of the Study:

  • To identify genetic suppressor elements (GSEs) that protect NIH3T3 cells from TNF-induced apoptosis.
  • To investigate the role of the identified gene, SDCCAG3, in TNF-mediated cell death and TNFR1 presentation.

Main Methods:

  • Utilized the genetic suppressor element (GSE) methodology to screen for protective genes in TNF-resistant cells.
  • Expressed a dominant-negative mutant of SDCCAG3 to assess its impact on TNF sensitivity and TNFR1 cell surface presentation.
  • Analyzed protein trafficking and secretion pathways affected by SDCCAG3 activity.

Main Results:

  • Isolated ten GSEs, with GSE0-1 identified as the mouse homolog of SDCCAG3.
  • SDCCAG3 protein shares a domain with proteins involved in organelle/protein trafficking.
  • Dominant-negative SDCCAG3 mutants conferred resistance to TNF-induced apoptosis by reducing TNFR1 presentation on the cell surface, linked to suppressed protein trafficking and secretion.

Conclusions:

  • SDCCAG3 plays a significant role in protein trafficking and the presentation of TNFR1 on the cell surface.
  • SDCCAG3 is a potential therapeutic target for modulating the cellular response to TNF.

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