Tal, a Tsg101-specific E3 ubiquitin ligase, regulates receptor endocytosis and retrovirus budding
- Ido Amit1,7,
- Liat Yakir1,7,
- Menachem Katz1,
- Yaara Zwang1,
- Mina D. Marmor1,
- Ami Citri1,
- Keren Shtiegman1,
- Iris Alroy2,
- Shmuel Tuvia2,
- Yuval Reiss2,
- Eli Roubini3,
- Maya Cohen3,
- Ron Wides4,
- Eran Bacharach5,
- Ullrich Schubert6, and
- Yosef Yarden1,8
- 1Department of Biological Regulation, The Weizmann Institute of Science, Rehovot 76100, Israel; 2Proteologics Ltd., Rehovot 76124, Israel; 3Sigma-Aldrich Israel, Ltd., Rehovot 76100, Israel; 4Department of Life Sciences, Bar-Ilan University, Ramat Gan 52900, Israel; 5Department of Cell Research and Immunology, Tel Aviv University, Tel Aviv 69978, Israel; 6Institute of Clinical and Molecular Virology, University of Erlangen-Nürnberg, 91054 Erlangen, Germany
Abstract
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.
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Footnotes
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Supplemental material is available at http://www.genesdev.org.
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Article and publication are at http://www.genesdev.org/cgi/doi/10.1101/gad.294904.
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↵7 These authors contributed equally to this work.
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↵8 Corresponding author. E-MAIL yosef.yarden{at}weizmann.ac.il; FAX 972-8-9342488.
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- Accepted May 18, 2004.
- Received December 12, 2003.
- Cold Spring Harbor Laboratory Press