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Updated: Jul 24, 2026

Preparation of Cell-lines for Conditional Knockdown of Gene Expression and Measurement of the Knockdown Effects on E4orf4-Induced Cell Death
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Preparation of Cell-lines for Conditional Knockdown of Gene Expression and Measurement of the Knockdown Effects on E4orf4-Induced Cell Death

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Human CARD4 protein is a novel CED-4/Apaf-1 cell death family member that activates NF-kappaB

J Bertin1, W J Nir, C M Fischer

  • 1Millennium Pharmaceuticals, Inc., Cambridge, Massachusetts 02139, USA. bertin@mpi.com

The Journal of Biological Chemistry
|May 1, 1999
PubMed

Insights

Researchers discovered CARD4, a novel protein that activates apoptosis and NF-kappaB signaling. This protein may play a role in the innate immune response, coordinating key cellular defense pathways.

Area of Science:

  • Molecular Biology
  • Immunology
  • Cell Biology

Background:

  • The nematode CED-4 and human Apaf-1 are key regulators of apoptosis, directly activating caspases.
  • Apoptosis is a critical process in cellular health and disease.
  • Plant disease resistance proteins share structural similarities with certain cytoplasmic signaling proteins.

Purpose of the Study:

  • To identify and characterize novel human homologs of CED-4/Apaf-1.
  • To investigate the signaling pathways and cellular functions of the newly identified protein, CARD4.
  • To determine the role of CARD4 in apoptosis and innate immunity.

Main Methods:

  • Protein identification and characterization.
  • Co-immunoprecipitation assays to study protein interactions.
  • Reporter gene assays to measure NF-kappaB activity.
  • Caspase activity assays and apoptosis assays.

Main Results:

  • A novel human CED-4/Apaf-1 family member, CARD4, was identified.
  • CARD4 interacts with the serine-threonine kinase RICK.
  • CARD4 induces NF-kappaB activity via TRAF-6 and NIK signaling.
  • Coexpression of CARD4 enhances caspase-9-induced apoptosis.

Conclusions:

  • CARD4 is a novel protein that links apoptosis and NF-kappaB signaling pathways.
  • CARD4 may function as a component of the host innate immune response.
  • The findings suggest CARD4 plays a dual role in cellular defense and programmed cell death.

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