The eps15 homology (EH) domain-based interaction between eps15 and hrb connects the molecular machinery of endocytosis to that of nucleocytosolic transport.
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.
Doria
M
M
Department of Experimental Oncology, European Institute of Oncology, 20141 Milan, Italy.
Salcini
A E
AE
Colombo
E
E
Parslow
T G
TG
Pelicci
P G
PG
Di Fiore
P P
PP
D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D001692:Biological Transport; D002135:Calcium-Binding Proteins / Q000502:physiology*; D002451:Cell Compartmentation / Q000502:physiology; D002460:Cell Line; D002467:Cell Nucleus / Q000378:metabolism / Q000502:physiology*; D003600:Cytosol / Q000502:physiology*; D004357:Drug Synergism; D004705:Endocytosis; D015694:Gene Products, rev / Q000502:physiology*; D028861:Nuclear Pore Complex Proteins; D009687:Nuclear Proteins / Q000502:physiology*; D010750:Phosphoproteins / Q000502:physiology*; D016601:RNA-Binding Proteins; D017386:Sequence Homology, Amino Acid; D015398:Signal Transduction
C119724:AGFG1 protein, human; D048868:Adaptor Proteins, Signal Transducing; D002135:Calcium-Binding Proteins; C094318:Eps15-rs protein, mouse; D015694:Gene Products, rev; D028861:Nuclear Pore Complex Proteins; D009687:Nuclear Proteins; D010750:Phosphoproteins; D016601:RNA-Binding Proteins