Tal, a Tsg101-specific E3 ubiquitin ligase, regulates receptor endocytosis and retrovirus budding.
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.
Amit
Ido
I
Department of Biological Regulation, The Weizmann Institute of Science, Rehovot 76100, Israel.
Yakir
Liat
L
Katz
Menachem
M
Zwang
Yaara
Y
Marmor
Mina D
MD
Citri
Ami
A
Shtiegman
Keren
K
Alroy
Iris
I
Tuvia
Shmuel
S
Reiss
Yuval
Y
Roubini
Eli
E
Cohen
Maya
M
Wides
Ron
R
Bacharach
Eran
E
Schubert
Ullrich
U
Yarden
Yosef
Y
D001483:Base Sequence; D001665:Binding Sites; D002478:Cells, Cultured; D003593:Cytoplasm / Q000378:metabolism / Q000502:physiology; D004268:DNA-Binding Proteins / Q000378:metabolism*; D004705:Endocytosis / Q000502:physiology*; D056827:Endosomal Sorting Complexes Required for Transport; D066246:ErbB Receptors / Q000378:metabolism; D005089:Exocytosis / Q000502:physiology*; D005455:Fluorescent Antibody Technique; D015723:Gene Library; D015683:Gene Products, gag / Q000378:metabolism; D006678:HIV / Q000378:metabolism*; D006801:Humans; D008969:Molecular Sequence Data; D010446:Peptide Fragments; D010957:Plasmids / Q000235:genetics; D021381:Protein Transport / Q000502:physiology; D034741:RNA, Small Interfering / Q000235:genetics; D017422:Sequence Analysis, DNA; D014157:Transcription Factors / Q000378:metabolism*; D014162:Transfection; D020798:Two-Hybrid System Techniques; D044767:Ubiquitin-Protein Ligases / Q000235:genetics* / Q000378:metabolism*; D014452:Ubiquitins / Q000378:metabolism; D000099177:Tsg101 Protein
D004268:DNA-Binding Proteins; D056827:Endosomal Sorting Complexes Required for Transport; D066246:ErbB Receptors; D015683:Gene Products, gag; D010446:Peptide Fragments; D034741:RNA, Small Interfering; D014157:Transcription Factors; D044767:Ubiquitin-Protein Ligases; D014452:Ubiquitins; D000099177:Tsg101 Protein; C489657:LRSAM1 protein, human