Functional screening of five PYPAF family members identifies PYPAF5 as a novel regulator of NF-kappaB and caspase-1

FEBS Lett. 2002 Oct 23;530(1-3):73-8. doi: 10.1016/s0014-5793(02)03416-6.


PYRIN-containing Apaf-1-like proteins (PYPAFs) are a recently identified family of proteins thought to function in apoptotic and inflammatory signaling pathways. PYPAF1 and PYPAF7 proteins have been found to assemble with the PYRIN-CARD protein ASC and coordinate the activation of NF-kappaB and pro-caspase-1. To determine if other PYPAF family members function in pro-inflammatory signaling pathways, we screened five other PYPAF proteins (PYPAF2, PYPAF3, PYPAF4, PYPAF5 and PYPAF6) for their ability to activate NF-kappaB and pro-caspase-1. Co-expression of PYPAF5 with ASC results in a synergistic activation of NF-kappaB and the recruitment of PYPAF5 to punctate structures in the cytoplasm. The expression of PYPAF5 is highly restricted to granulocytes and T-cells, indicating a role for this protein in inflammatory signaling. In contrast, PYPAF2, PYPAF3, PYPAF4 and PYPAF6 failed to colocalize with ASC and activate NF-kappaB. PYPAF5 also synergistically activated caspase-1-dependent cytokine processing when co-expressed with ASC. These findings suggest that PYPAF5 functions in immune cells to coordinate the transduction of pro-inflammatory signals to the activation of NF-kappaB and pro-caspase-1.

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Base Sequence
  • COS Cells
  • Carrier Proteins / chemistry
  • Carrier Proteins / genetics
  • Carrier Proteins / metabolism
  • Carrier Proteins / physiology*
  • Caspase 1 / physiology*
  • Cell Line
  • DNA Primers
  • Enzyme Activation
  • Humans
  • Intracellular Signaling Peptides and Proteins*
  • Leukocytes / metabolism
  • Molecular Sequence Data
  • NF-kappa B / physiology*
  • Signal Transduction


  • Carrier Proteins
  • DNA Primers
  • Intracellular Signaling Peptides and Proteins
  • NF-kappa B
  • NLRP6 protein, human
  • Caspase 1