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

被引:237
作者
Richards, N
Schaner, P
Diaz, A
Stuckey, J
Shelden, E
Wadhwa, A
Gumucio, DL
机构
[1] Univ Michigan, Sch Med, Dept Cell & Dev Biol, Ann Arbor, MI 48109 USA
[2] Univ Michigan, Sch Med, Dept Internal Med, Ann Arbor, MI 48109 USA
[3] Univ Michigan, Sch Med, Dept Biochem, Ann Arbor, MI 48109 USA
[4] Univ Michigan, Sch Med, Grad Program Cellular & Mol Biol, Ann Arbor, MI 48109 USA
关键词
D O I
10.1074/jbc.M104730200
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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 deck 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.
引用
收藏
页码:39320 / 39329
页数:10
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