Abstract

The nematode CED-4 protein and its human homolog Apaf-1 play a central role in apoptosis by functioning as direct activators of death-inducing caspases. A novel human CED-4/Apaf-1 family member called CARD4 was identified that has a domain structure strikingly similar to the cytoplasmic, receptor-like proteins that mediate disease resistance in plants. CARD4 interacted with the serine-threonine kinase RICK and potently induced NF-kappaB activity through TRAF-6 and NIK signaling molecules. In addition, coexpression of CARD4 augmented caspase-9-induced apoptosis. Thus, CARD4 coordinates downstream NF-kappaB and apoptotic signaling pathways and may be a component of the host innate immune response.

Highlights

  • The nucleotide sequence(s) reported in this paper has been submitted to the GenBankTM/EBI Data Bank with accession number(s) AF126484

  • CARD4, a Novel CED-4/Apaf-1 Family Member taining proteins identified from the expressed sequence tags (EST) search

  • The N-terminal region of CARD4 shares significant sequence similarity with CARD motifs found in a variety of apoptotic signaling molecules, including those found in CED-4 and Apaf-1 (Fig. 1B)

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Summary

Introduction

The nucleotide sequence(s) reported in this paper has been submitted to the GenBankTM/EBI Data Bank with accession number(s) AF126484. The presence of CARD motifs in a variety of other effector and signaling molecules, including numerous caspases [6] and a recently identified NF-␬B-activating kinase [7,8,9], suggests that other CED-4/Apaf-1 family members likely exist in humans to coordinate downstream stress responses. We report here the identity and characterization of a novel human CED-4/Apaf-1 family member that activates NF-␬B and apoptotic signaling pathways.

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