| First Author | Atianand MK | Year | 2011 |
| Journal | J Biol Chem | Volume | 286 |
| Issue | 47 | Pages | 40536-47 |
| PubMed ID | 21976665 | Mgi Jnum | J:390804 |
| Mgi Id | MGI:6708807 | Doi | 10.1074/jbc.M111.274290 |
| Citation | Atianand MK, et al. (2011) Uncoupling of Pyrin-only protein 2 (POP2)-mediated dual regulation of NF-kappaB and the inflammasome. J Biol Chem 286(47):40536-47 |
| abstractText | Activation of transcription factor NF-kappaB and inflammasome-directed caspase-1 cleavage of IL-1beta are key processes in the inflammatory response to pathogen or host-derived signals. Pyrin-only proteins (POPs) are restricted to Old World monkeys, apes, and humans and have previously been shown to impair inflammasome assembly and/or NF-kappaB p65 transcriptional activity in transfected epithelial cells. However, the biological role of POP2 and the molecular basis for its observed functions are not well understood. In this report we demonstrate that POP2 regulates TNFalpha and IL-1beta responses in human monocytic THP-1 cells and in stable transfectants of mouse J774A.1 macrophages. Deletion analysis of POP2 revealed that the first alpha-helix (residues 1-19) is necessary and sufficient for both inflammasome and NF-kappaB inhibitory functions. Further, key acidic residues Glu(6), Asp(8), and Glu(16), believed critical for Pyrin/Pyrin domain interaction, are important for inflammasome inhibition. Moreover, these mutations did not reduce the effect of POP2 upon NF-kappaB, indicating that the inflammasome and NF-kappaB inhibitory properties of POP2 can be uncoupled mechanistically. Collectively, these data demonstrate that POP2 acts as a regulator of inflammatory signals and exerts its two known functions through distinct modalities employed by its first alpha-helix. |
