Document Actions
Mammalian tumor susceptibility gene 101 ... n in late endosomal trafficking
Mammalian tumor susceptibility gene 101 (TSG101) and the yeast homologue, Vps23p, both function in late endosomal trafficking.
29
The mammalian tumor susceptibility gene tsg101 encodes the homologue of Vps23p, a class E Vps protein essential for normal membrane trafficking in the late endosome/multivesicular body of yeast. Both proteins assemble into large (approximately 350 kDa) cytosolic protein complexes and we show that the yeast complex contains another class E Vps protein, Vps28p. tsg101 mutant cells exhibit defects in sorting and proteolytic maturation of the lysosomal hydrolase cathepsin D, as well as in the steady-state distribution of the mannose-6-phosphate receptor. Additionally, endocytosed EGF receptors that are normally sorted to the lysosome are instead rapidly recycled back to the cell surface in tsg101 mutant cells. We propose that tsg101 mutant cells are defective in the delivery of cargo proteins to late endosomal compartments. One consequence of this endosomal trafficking defect is the delayed down-regulation/degradation of activated cell surface receptors, resulting in prolonged signaling. This may contribute to the tumorigenic phenotype exhibited by the tsg101 mutant fibroblasts.
Babst M, Odorizzi G, Estepa EJ, Emr SD
Traffic (Copenhagen, Denmark)
2000-03-01 00:00
1
3
248-58
3T3 Cells,Amino Acid Sequence,Animals,Carrier Proteins,Cathepsin D,DNA-Binding Proteins,Endocytosis,Endosomes,Fungal Proteins,Lysosomes,MAP Kinase Signaling System,Macromolecular Substances,Mice,Molecular Sequence Data,Protein Transport,Receptor Protein-Tyrosine Kinases,Receptor, Epidermal Growth Factor,Receptor, IGF Type 2,Receptors, Transferrin,Recombinant Fusion Proteins,Saccharomyces cerevisiae,Saccharomyces cerevisiae Proteins,Sequence Alignment,Sequence Homology, Amino Acid,Transcription Factors,Vesicular Transport Proteins,Carrier Proteins,DNA-Binding Proteins,Fungal Proteins,Macromolecular Substances,Receptor, IGF Type 2,Receptors, Transferrin,Recombinant Fusion Proteins,STP22 protein, S cerevisiae,Saccharomyces cerevisiae Proteins,Transcription Factors,Tsg101 protein,VPS28 protein, S cerevisiae,Vesicular Transport Proteins,Receptor Protein-Tyrosine Kinases,Receptor, Epidermal Growth Factor,Cathepsin D
Division of Cellular and Molecular Medicine and Howard Hughes Medical Institute, School of Medicine, University of California at San Diego, La Jolla, CA 92093-0668, USA
Traffic
NCI CA 58689
1398-9219
tra010307
839
True
11208108
