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

Genes Dev. 2004 Jul 15;18(14):1737-52. doi: 10.1101/gad.294904.

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.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Base Sequence
  • Binding Sites
  • Cells, Cultured
  • Cytoplasm / metabolism
  • Cytoplasm / physiology
  • DNA-Binding Proteins / metabolism*
  • Endocytosis / physiology*
  • Endosomal Sorting Complexes Required for Transport
  • ErbB Receptors / metabolism
  • Exocytosis / physiology*
  • Fluorescent Antibody Technique
  • Gene Library
  • Gene Products, gag / metabolism
  • HIV / metabolism*
  • Humans
  • Molecular Sequence Data
  • Peptide Fragments
  • Plasmids / genetics
  • Protein Transport / physiology
  • RNA, Small Interfering / genetics
  • Sequence Analysis, DNA
  • Transcription Factors / metabolism*
  • Transfection
  • Two-Hybrid System Techniques
  • Ubiquitin-Protein Ligases / genetics*
  • Ubiquitin-Protein Ligases / metabolism*
  • Ubiquitins / metabolism

Substances

  • DNA-Binding Proteins
  • Endosomal Sorting Complexes Required for Transport
  • Gene Products, gag
  • Peptide Fragments
  • RNA, Small Interfering
  • Transcription Factors
  • Tsg101 protein
  • Ubiquitins
  • LRSAM1 protein, human
  • Ubiquitin-Protein Ligases
  • ErbB Receptors