The estrogen-responsive B box protein: a novel enhancer of interleukin-1beta secretion.
The estrogen-responsive B box protein (EBBP) and Pyrin belong to a family of structurally related proteins. While mutations in the pyrin gene cause an autoinflammatory disease, the biological function of EBBP is unknown. In this study, we identified the proinflammatory cytokine interleukin-1beta (IL-1beta) as an EBBP-binding partner. Furthermore, caspase-1 and NACHT, LRR and Pyrin domain containing protein (NALP) 1, two components of the recently identified inflammasome, a platform for the activation of caspase-1, also interact with EBBP. These proteins bind to the RFP domain of EBBP, suggesting that this domain of so far unknown function is an important protein-binding domain. EBBP was secreted in a caspase-1-dependent manner from cultured cells, and its secretion was enhanced by IL-1beta. Vice versa, endogenous and overerexpressed EBBP increased IL-1beta secretion. These results provide evidence for a role of EBBP in innate immunity by enhancing the alternative secretion pathway of IL-1beta.
Department of Biology, Institute of Cell Biology, ETH Zurich, ETH Honggerberg, CH-8093 Zurich, Switzerland.
C
C
Munding
M
M
Keller
G
G
Niklaus
S
S
Papin
J
J
Tschopp
S
S
Werner
H-D
HD
Beer
D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism; D000818:Animals; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism; D019556:COS Cells; D020170:Caspase 1 / Q000378:metabolism; D002522:Chlorocebus aethiops; D003598:Cytoskeletal Proteins / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000378:metabolism*; D004967:Estrogens / Q000494:pharmacology; D006801:Humans; D053583:Interleukin-1beta / Q000378:metabolism*; D000070576:NLR Proteins; D011485:Protein Binding; D011498:Protein Precursors / Q000378:metabolism; D017434:Protein Structure, Tertiary; D014157:Transcription Factors / Q000378:metabolism*; D014162:Transfection; D000070584:Tripartite Motif Proteins; D044767:Ubiquitin-Protein Ligases
D048868:Adaptor Proteins, Signal Transducing; D051017:Apoptosis Regulatory Proteins; D003598:Cytoskeletal Proteins; D004268:DNA-Binding Proteins; D004967:Estrogens; D053583:Interleukin-1beta; D000070576:NLR Proteins; C427903:NLRP1 protein, human; D011498:Protein Precursors; D014157:Transcription Factors; D000070584:Tripartite Motif Proteins; C117731:TRIM16 protein, human; D044767:Ubiquitin-Protein Ligases; D020170:Caspase 1