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© The Rockefeller University Press, 0021-9525/1999/12/1379/ $5.00
The Journal of Cell Biology, Volume 147, Number 7, December 27, 1999 1379-1384


Brief Report

The Eps15 Homology (EH) Domain-based Interaction between Eps15 and Hrb Connects the Molecular Machinery of Endocytosis to That of Nucleocytosolic Transport

Margherita Doriaa, Anna Elisabetta Salcinia, Emanuela Colomboa, Tristram G. Parslowb, Pier Giuseppe Peliccia,c, and Pier Paolo Di Fiorea,d
a Department of Experimental Oncology, European Institute of Oncology, 20141 Milan, Italy
b Department of Pathology, University of California, San Francisco California 94193
c Istituto di Patologia Speciale Medica, University of Parma, 43100 Italy
d Istituto di Microbiologia, University of Bari, 70123 Italy

Correspondence to: Pier Paolo Di Fiore, Istituto Europeo di Oncologia, Via Ripamonti 435, 20141 Milan, Italy. Tel:39-02-57489855 Fax:39-02-57489851 E-mail:pdifiore{at}ieo.it.

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.

Key Words: EH, Eps15, Hrb, endocytosis, nucleocytoplasmic transport


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