J Biol Chem. 2001 Oct 19;276(42):39320-9. Epub 2001 Aug 9.

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

Richards, N., Schaner, P., Diaz, A., Stuckey, J., Shelden, E., Wadhwa, A., Gumucio, D. L.,
--- - Department of Cell and Developmental Biology, The University of Michigan Medical School, Ann Arbor, Michigan, 48109-0616, USA.
Patients with familial Mediterranean fever suffer sporadic inflammatory attacks characterized by fever and intense pain (in joints, abdomen, or chest). Pyrin, the product of the MEFV locus, is a cytosolic protein whose function is unknown. Using pyrin as a "bait" to probe a yeast two-hybrid library made from neutrophil cDNA, we isolated apoptotic speck protein containing a caspase recruitment domain (CARD) (ASC), a proapoptotic protein that induces the formation of large cytosolic "specks" in transfected cells. We found that when HeLa cells are transfected with ASC, specks are formed. After co-transfection of cells with ASC plus wild type pyrin, an increase in speck-positive cells is found, and speck-positive cells show increased survival. Immunofluorescence studies show that pyrin co-localizes with ASC in specks. Speck localization requires exon 1 of pyrin, but exon 1 alone of pyrin does not result in an increase in the number of specks. Exon 1 of pyrin and exon 1 of ASC show 42% sequence similarity and resemble death domain-related structures in modeling studies. These findings link pyrin to apoptosis pathways and suggest that the modulation of cell survival may be a component of the pathophysiology of familial Mediterranean fever.
PMID: 11498534External
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
PYD ASC Link Pyrin Co-Immunofluorescence staining HeLa Not specified Not specified Not specified Not specified 11498534
(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 DAPI staining Apoptosis inhibition 11498534
(Link: click this icon to show interactions only between the two corresponding DDs)