Targeting of AMSH to endosomes is required for epidermal growth factor receptor degradation.
To reach the lysosomes, down-regulated receptors such as the epidermal growth factor receptor must first be sorted into internal vesicles of late endosomes (multivesicular bodies), a ubiquitin-dependent event that requires the coordinated function of the endosome sorting complex required for transport (ESCRT) proteins. Here we report that CHMP3, an ESCRT-III ... complex component, and associated molecule of SH3 domain of STAM (AMSH), a deubiquitinating enzyme, interact with each other in cells. A dominant-negative version of CHMP3, which specifically prevents targeting of AMSH to endosomes, inhibits degradation but not internalization of EGFR, suggesting that endosomal AMSH is a functional component of the multivesicular body pathway.
Mesh Terms:
Amino Acid Sequence, Animals, COS Cells, Cercopithecus aethiops, Endosomal Sorting Complexes Required for Transport, Endosomes, Hela Cells, Humans, Molecular Sequence Data, Nerve Tissue Proteins, Protein Transport, Receptor, Epidermal Growth Factor, Signal Transduction, Ubiquitin Thiolesterase
Amino Acid Sequence, Animals, COS Cells, Cercopithecus aethiops, Endosomal Sorting Complexes Required for Transport, Endosomes, Hela Cells, Humans, Molecular Sequence Data, Nerve Tissue Proteins, Protein Transport, Receptor, Epidermal Growth Factor, Signal Transduction, Ubiquitin Thiolesterase
J. Biol. Chem.
Date: Mar. 30, 2007
PubMed ID: 17261583
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