Epsin 1 undergoes nucleocytosolic shuttling and its Eps15 interactor NH2-terminal homology (ENTH) domain, structurally similar to Armadillo and HEAT repeats, interacts with the transcription factor promyelocytic leukemia Zn2+ finger protein (PLZF)

Abstract

Epsin (Eps15 interactor) is a cytosolic protein involved in clathrin- mediated endocytosis via its direct interactions with clathrin, the clathrin adaptor AP-2, and Eps15. The NH2-terminal portion of epsin contains a phylogenetically conserved module of unknown function, known as the ENTH domain (epsin NH2-terminal homology domain). We have now solved the crystal structure of rat epsin 1 ENTH domain to 1.8 Å resolution. This domain is structurally similar to armadillo and Heat repeats of β-catenin and karyopherin-β, respectively. We have also identified and characterized the interaction of epsin 1, via the ENTH domain, with the transcription factor promyelocytic leukemia Zn2+ finger protein (PLZF). Leptomycin B, an antifungal antibiotic, which inhibits the Crm1-dependent nuclear export pathway, induces an accumulation of epsin 1 in the nucleus. These findings suggest that epsin 1 may function in a signaling pathway connecting the endocytic machinery to the regulation of nuclear function.