Pyrin-Only Protein 2 Modulates NF-κB and Disrupts ASC:CLR Interactions

摘要: NF-κB is pivotal for transactivation of cell-cycle regulatory, cytokine, and adhesion molecule genes dysregulated in many cancers, neurodegenerative disorders, inflammatory diseases. Proteins with pyrin and/or caspase recruitment domains have roles apoptosis, innate immunity, inflammation. Many domain (PYD) proteins modulate activity as well participate assembling both the perinuclear “apoptotic speck” pro-IL1β/IL-18-converting inflammasome complex. “Pyrin-only” (POP) are attractive negative regulators PYD-mediated functions one such protein, POP1, has been reported. We report identification initial characterization a second POP. POP2 294 nt single exon gene located on human chromosome 3 encoding 97-aa protein sequence predicted structural similarity to other PYDs. Highly similar PYDs CATERPILLER (CLR, NLR, NALP) family proteins, less like prototypic ASC expressed principally peripheral blood leukocytes displays cytoplasmic nuclear expression patterns transfected cells. TNF-α-stimulated p65 (RelA)-induced NF-κB-dependent transcription inhibited by vitro mechanism involving changes import or distribution. While colocalizing specks, also inhibits formation specks CLR CIAS1/NALP3. Together, these observations demonstrate that regulator may influence assembly PYD-dependent complexes.