The Eps15 homology (EH) domain-based interaction between Eps15 and Hrb connects the molecular machinery of endocytosis to that of nucleocytosolic transport

• Type of Material: Article
• Authors: Margherita Doria, European Institute of Oncology; Anna Elisabetta Salcini, European Institute of Oncology; Emanuela Colombo, European Institute of Oncology; Tristram G Parslow, Emory University; Pier Giuseppe Pelicci, European Institute of Oncology; Pier Paolo Di Fiore, European Institute of Oncology
• Language: English
• Date: 1999-12-27
• Publisher: Rockefeller University Press
• Publication Version: Final Published Version
• Copyright Statement: © 1999 The Rockefeller University Press
• License: Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1083/jcb.147.7.1379
• Title of Journal or Parent Work: Journal of Cell Biology
• ISSN: 0021-9525
• Volume: 147
• Issue: 7
• Start Page: 1379
• End Page: 1384
• Grant/Funding Information: This work was supported by grants from Istituto Superiore della Sanita' (AIDS 1998), from the National Institutes of Health (AI40317), from Associazione Italiana Ricerca sul Cancro, from Fondazione Telethon, and from the Armenise-Harvard Foundation. M. Doria is the recipient of a fellowship from the Fondazione Vollaro.
• Keywords: BINDING; Eps15; PROTEIN EXPORT PATHWAY; EH; IDENTIFICATION; NUCLEAR EXPORT; RNAS; Hrb; HUMAN-IMMUNODEFICIENCY-VIRUS; Science & Technology; IMPORTIN-BETA; Cell Biology; endocytosis; Life Sciences & Biomedicine; TYPE-1 REV PROTEIN; HIV REV; TYROSINE KINASE SUBSTRATE; nucleocytoplasmic transport
• Research Categories: Health Sciences, Oncology; Health Sciences, Pathology

Abstract

The Eps15 homology (EH) module is a protein-protein interaction domain that establishes a network of connections involved in various aspects of endocytosis and sorting. The finding that EH-containing proteins bind to Hrb (a cellular cofactor of the Rev protein) and to the related protein Hrbl raised the possibility that the EH network might also influence the so-called Rev export pathway, which mediates nucleocytoplasmic transfer of proteins and RNAs. In this study, we demonstrate that Eps15 and Eps15R, two EH-containing proteins, synergize with Hrb and Hrbl to enhance the function of Rev in the export pathway. In addition, the EH-mediated association between Eps15 and Hrb is required for the synergistic effect. The interaction between Eps15 and Hrb occurs in the cytoplasm, thus pointing to an unexpected site of action of Hrb, and to a possible role of the Eps15-Hrb complex in regulating the stability of Rev.