Pyrin-only protein 3: a pseudogene product in the human genome regulating NF-kB activity (157.4)

Abstract

Abstract Pyrin-only proteins influence NF-kB and inflammasome signaling pathways. In viruses, POPs act as pathogenic factors by reducing innate immune responses and favoring viral survival within the host. In humans, two known POPs are thought to have a role in regulating innate immunity and inflammation. POP1 interferes with IKKα/β activation and prevents the downstream activation of NF-kB with no known effect on ASC-dependent inflammasomes. POP2 however, inhibits NF-kB signaling at the level of the p65 (RelA) subunit and down-modulates the formation and activation of a variety of pyrin domain/ASC-dependent inflammasomes. Here we describe a third human POP, POP3, the product of an NLRP pseudogene encoded on chromosome X that is expressed in a wide variety of tissues. Like its close genetic relative POP2, POP3 inhibits p65 activation downstream of IKK, but lacks the capacity of inhibit the NLRP3 inflammasome. Our data suggest that the human POP family has three members, all of which may play distinct biological roles during inflammation.