Related Experiment Video

Updated: Sep 26, 2026

Determination of the Relative Potency of an Anti-TNF Monoclonal Antibody (mAb) by Neutralizing TNF Using an In Vitro Bioanalytical Method
16:07

Determination of the Relative Potency of an Anti-TNF Monoclonal Antibody (mAb) by Neutralizing TNF Using an In Vitro Bioanalytical Method

Published on: September 16, 2017

Role of SODD in regulation of tumor necrosis factor responses

Hidetoshi Takada1, Nien-Jung Chen, Christine Mirtsos

  • 1Advanced Medical Discovery Institute, University Health Network, Department of Medical Biophysics, University of Toronto, Toronto, Ontario, Canada M5G 2C1.

Molecular and Cellular Biology
|May 16, 2003
PubMed

Insights

Silencer of death domains (SODD) protein regulates tumor necrosis factor receptor type 1 (TNFR1) signaling. SODD deficiency in mice leads to increased cytokine production and altered cellular responses to TNF, highlighting SODD's critical regulatory role.

Area of Science:

  • Immunology
  • Molecular Biology
  • Cellular Signaling

Background:

  • Tumor necrosis factor receptor type 1 (TNFR1) signaling triggers inflammatory and cytotoxic responses.
  • The silencer of death domains (SODD) protein is hypothesized to constitutively bind TNFR1, preventing spontaneous signaling complex formation.

Purpose of the Study:

  • To investigate the role of SODD in regulating TNFR1 signaling pathways.
  • To determine the in vivo and in vitro consequences of SODD deficiency on TNF-induced responses.

Main Methods:

  • Generation and analysis of SODD-deficient mice.
  • Assessment of cytokine production in response to TNF challenge in vivo.
  • Examination of TNF-induced signaling pathways (NF-kappaB, c-Jun N-terminal kinase) in SODD-deficient cells (macrophages, fibroblasts).

Main Results:

  • SODD-deficient mice exhibit elevated cytokine production following TNF challenge.
  • SODD-deficient cells show accelerated TNF-induced NF-kappaB activation.
  • TNF-induced c-Jun N-terminal kinase activity is diminished in SODD-deficient cells.
  • Apoptotic responses to TNF are not enhanced in the absence of SODD.

Conclusions:

  • SODD plays a crucial role in the fine-tuning of TNFR1 signaling.
  • SODD acts as a negative regulator for specific TNF-induced inflammatory pathways, but not apoptosis.

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