Mol Cell. 2003 Mar;11(3):591-604.

Targeted disruption of pyrin, the FMF protein, causes heightened sensitivity to endotoxin and a defect in macrophage apoptosis.External

Chae, J. J., Komarow, H. D., Cheng, J., Wood, G., Raben, N., Liu, P. P., Kastner, D. L.,
--- - Inflammatory Biology Section, Genetics and Genomics Branch, National Institute of Arthritis and Musculoskeletal and Skin Diseases, Bethesda, MD 20892, USA. chaej@exchange.nih.gov
Familial Mediterranean fever (FMF) is an inherited disorder characterized by recurrent episodes of fever and inflammation. Most patients with FMF carry missense mutations in the C-terminal half of the pyrin protein. To study the physiologic role of pyrin, we generated mice expressing a truncated pyrin molecule that, similar to FMF patients, retains the full PYRIN domain. Bacterial lipopolysaccharide (LPS) induces accentuated body temperatures and increased lethality in homozygous mutant mice. When stimulated, macrophages from these mice produce increased amounts of activated caspase-1 and, consequently, elevated levels of mature IL-1beta. Full-length pyrin competes in vitro with caspase-1 for binding to ASC, a known caspase-1 activator. Apoptosis is impaired in macrophages from pyrin-truncation mice through an IL-1-independent pathway. These data support a critical role for pyrin in the innate immune response, possibly by acting on ASC, and suggest a biologic basis for the selection of hypomorphic pyrin variants in man.
PMID: 12667444External
Arrow2 In vitro interaction Arrow2 In vivo interaction Arrow2 Characterization Arrow2 Functional role Arrow2 top
In vivo interaction
  Endogenous
expression
Overexpression DD1 DD2 Reference
Family DD1 DD2 Method Species Region Species Region
CARD ASC Link Caspase1 Co-immunoprecipitation PT67 Mouse Full length Mouse Not specified 12667444
CARD ASC Link Caspase1 GST fusion protein pull-down PT67 Mouse Full length Mouse Not specified 12667444
PYD ASC Link Pyrin Co-Immunofluorescence staining PT67 Mouse Full length Mouse Full length 12667444
PYD ASC Link Pyrin GST fusion protein pull-down PT67 Mouse Full length Mouse Not specified 12667444
(Link: click this icon to show interactions only between the two corresponding DDs)
Arrow2 In vitro interaction Arrow2 In vivo interaction Arrow2 Characterization Arrow2 Functional role Arrow2 top
Functional Role
Family DD1 DD2 Method Death-related Death-unrelated Reference
PYD ASC Link Pyrin Apoptotic DNA ladder assay Apoptosis inhibition 12667444
(Link: click this icon to show interactions only between the two corresponding DDs)