1. ¹Department of Biology, Institute of Cell Biology, ETH Zurich, ETH Honggerberg, CH-8093 Zurich, Switzerland
2. ²Institute of Biochemistry, BIL Biomedical Research Center, University of Lausanne, CH-1066 Epalinges, Switzerland
3. ³Current address: King's College London, Guy's Campus, New Hunt's House, The Randall Centre, London SE1 1UL, UK
4. ⁴These authors have equally contributed to this work

Correspondence: H-D Beer, Institute of Cell Biology, HPM D44, ETH Zurich, Honggerberg, CH-8093 Zurich, Switzerland. Tel: +41-1-6333405; Fax: +41-1-6331174; E-mail: dietmar.beer@cell.biol.ethz.ch

Received 24 August 2005; Revised 14 February 2006; Accepted 15 February 2006; Published online 31 March 2006.

Abstract

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-1 (IL-1) 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-1. Vice versa, endogenous and overerexpressed EBBP increased IL-1 secretion. These results provide evidence for a role of EBBP in innate immunity by enhancing the alternative secretion pathway of IL-1.