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Interaction between pyrin and the apoptotic speck protein (ASC) modulates ASC-induced apoptosis

N Richards1, P Schaner, A Diaz

  • 1Department of Cell and Developmental Biology, The University of Michigan Medical School, Ann Arbor, Michigan, 48109-0616, USA.

The Journal of Biological Chemistry
|August 11, 2001
PubMed

Insights

Familial Mediterranean fever protein pyrin interacts with ASC, forming cellular specks. This interaction enhances cell survival, suggesting a role in the disease

Area of Science:

  • Molecular Biology
  • Immunology
  • Cell Biology

Background:

  • Familial Mediterranean fever (FMF) is characterized by inflammatory attacks.
  • Pyrin, the FMF protein, is cytosolic, and its function is unknown.
  • Apoptotic speck protein containing a caspase recruitment domain (ASC) is a proapoptotic protein.

Purpose of the Study:

  • To investigate the function of pyrin.
  • To explore the interaction between pyrin and ASC.
  • To understand the role of this interaction in FMF pathophysiology.

Main Methods:

  • Yeast two-hybrid screening using pyrin as bait.
  • Transfection of HeLa cells with ASC and pyrin.
  • Immunofluorescence studies to assess co-localization.
  • Sequence similarity and modeling studies of pyrin and ASC domains.

Main Results:

  • Pyrin interacts with ASC, forming large cytosolic specks.
  • Co-transfection of ASC and pyrin increases speck-positive cells.
  • Speck-positive cells exhibit enhanced survival.
  • Pyrin co-localizes with ASC in specks, requiring exon 1 of pyrin.
  • Exon 1 of pyrin and ASC share sequence similarity and structural resemblance to death domains.

Conclusions:

  • Pyrin is linked to apoptosis pathways through its interaction with ASC.
  • Modulation of cell survival may be involved in the pathophysiology of familial Mediterranean fever.
  • The findings provide new insights into the molecular mechanisms of FMF.

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