Tal, a Tsg101-specific E3 ubiquitin ligase, regulates receptor endocytosis and retrovirus budding

  1. Ido Amit1,7,
  2. Liat Yakir1,7,
  3. Menachem Katz1,
  4. Yaara Zwang1,
  5. Mina D. Marmor1,
  6. Ami Citri1,
  7. Keren Shtiegman1,
  8. Iris Alroy2,
  9. Shmuel Tuvia2,
  10. Yuval Reiss2,
  11. Eli Roubini3,
  12. Maya Cohen3,
  13. Ron Wides4,
  14. Eran Bacharach5,
  15. Ullrich Schubert6, and
  16. Yosef Yarden1,8
  1. 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.

Keywords

Footnotes

  • Supplemental material is available at http://www.genesdev.org.

  • 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.

    • Accepted May 18, 2004.
    • Received December 12, 2003.
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