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RESEARCH PAPER
1 Department of Biological Regulation, The Weizmann Institute of Science, Rehovot 76100, Israel; 2 Proteologics Ltd., Rehovot 76124, Israel; 3 Sigma-Aldrich Israel, Ltd., Rehovot 76100, Israel; 4 Department of Life Sciences, Bar-Ilan University, Ramat Gan 52900, Israel; 5 Department of Cell Research and Immunology, Tel Aviv University, Tel Aviv 69978, Israel; 6 Institute of Clinical and Molecular Virology, University of Erlangen-Nürnberg, 91054 Erlangen, Germany
The tumor suppressor gene 101 (tsg101) regulates vesicular trafficking processes in yeast and mammals. We report a novel protein, Tal (Tsg101-associated ligase), whose RING finger is necessary for multiple monoubiquitylation of Tsg101. Bivalent binding of Tsg101 to a tandem tetrapeptide motif (PTAP) and to a central region of Tal is essential for Tal-mediated ubiquitylation of Tsg101. By studying endocytosis of the epidermal growth factor receptor and egress of the human immunodeficiency virus, we conclude that Tal regulates a Tsg101-associated complex responsible for the sorting of cargo into cytoplasm-containing vesicles that bud at the multivesicular body and at the plasma membrane.
[Keywords: Endocytosis; growth factor; HIV; ubiquitin; signal transduction]
Received December 12, 2003; revised version accepted May 18, 2004.
Article and publication are at http://www.genesdev.org/cgi/doi/10.1101/gad.294904.
7 These authors contributed equally to this work.
8 Corresponding author.
E-MAIL yosef.yarden{at}weizmann.ac.il; FAX 972-8-9342488.
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