title: Epsin 1 undergoes nucleocytosolic shuttling and its eps15 interactor NH(2)-terminal homology (ENTH) domain, structurally similar to Armadillo and HEAT repeats, interacts with the transcription factor promyelocytic leukemia Zn(2)+ 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 NH(2)-terminal portion of epsin contains a phylogenetically conserved module of unknown function, known as the ENTH domain (epsin NH(2)-terminal homology domain). We have now solved the crystal structure of rat epsin 1 ENTH domain to 1.8 A resolution. This domain is structurally similar to armadillo and Heat repeats of beta-catenin and karyopherin-beta, respectively. We have also identified and characterized the interaction of epsin 1, via the ENTH domain, with the transcription factor promyelocytic leukemia Zn(2)+ 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.
authors.affiliation: Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, Connecticut 06520, USA.
authors.forename: J
authors.initials: J
authors.lastname: Hyman
authors.forename: H
authors.initials: H
authors.lastname: Chen
authors.forename: P P
authors.initials: PP
authors.lastname: Di Fiore
authors.forename: P
authors.initials: P
authors.lastname: De Camilli
authors.forename: A T
authors.initials: AT
authors.lastname: Brunger
mesh_terms: D033942:Adaptor Proteins, Vesicular Transport; D000595:Amino Acid Sequence; D000818:Animals; D051186:Armadillo Domain Proteins; D002135:Calcium-Binding Proteins / Q000378:metabolism*; D002352:Carrier Proteins / Q000737:chemistry* / Q000378:metabolism; D002460:Cell Line; D002467:Cell Nucleus / Q000378:metabolism; D018360:Crystallography, X-Ray; D003598:Cytoskeletal Proteins / Q000737:chemistry; D003600:Cytosol / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000378:metabolism*; D029721:Drosophila Proteins; D005455:Fluorescent Antibody Technique; D019476:Insect Proteins / Q000737:chemistry; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009479:Neuropeptides / Q000737:chemistry* / Q000378:metabolism; D010750:Phosphoproteins / Q000378:metabolism*; D011485:Protein Binding; D051381:Rats; D016415:Sequence Alignment; D015534:Trans-Activators; D014157:Transcription Factors / Q000378:metabolism*; D033921:Vesicular Transport Proteins; D016335:Zinc Fingers; D051176:beta Catenin
chemical_list: D033942:Adaptor Proteins, Vesicular Transport; D051186:Armadillo Domain Proteins; D002135:Calcium-Binding Proteins; D002352:Carrier Proteins; C495268:Ctnnb1 protein, rat; D003598:Cytoskeletal Proteins; D004268:DNA-Binding Proteins; D029721:Drosophila Proteins; D019476:Insect Proteins; D009479:Neuropeptides; D010750:Phosphoproteins; D015534:Trans-Activators; D014157:Transcription Factors; D033921:Vesicular Transport Proteins; D051176:beta Catenin; C114154:epsin