| The ESCRT-III subunit hVps24 is required for degradation but not silencing of the epidermal growth factor receptor. | |
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MedLine Citation:
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PMID: 16554368 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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The endosomal sorting complexes required for transport, ESCRT-I, -II, and -III, are thought to mediate the biogenesis of multivesicular endosomes (MVEs) and endosomal sorting of ubiquitinated membrane proteins. Here, we have compared the importance of the ESCRT-I subunit tumor susceptibility gene 101 (Tsg101) and the ESCRT-III subunit hVps24/CHMP3 for endosomal functions and receptor signaling. Like Tsg101, endogenous hVps24 localized mainly to late endosomes. Depletion of hVps24 by siRNA showed that this ESCRT subunit, like Tsg101, is important for degradation of the epidermal growth factor (EGF) receptor (EGFR) and for transport of the receptor from early endosomes to lysosomes. Surprisingly, however, whereas depletion of Tsg101 caused sustained EGF activation of the mitogen-activated protein kinase pathway, depletion of hVps24 had no such effect. Moreover, depletion of Tsg101 but not of hVps24 caused a major fraction of internalized EGF to accumulate in nonacidified endosomes. Electron microscopy of hVps24-depleted cells showed an accumulation of EGFRs in MVEs that were significantly smaller than those in control cells, probably because of an impaired fusion with lyso-bisphosphatidic acid-positive late endosomes/lysosomes. Together, our results reveal functional differences between ESCRT-I and ESCRT-III in degradative protein trafficking and indicate that degradation of the EGFR is not required for termination of its signaling. |
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Authors:
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Kristi G Bache; Susanne Stuffers; Lene Malerød; Thomas Slagsvold; Camilla Raiborg; Delphine Lechardeur; Sébastien Wälchli; Gergely L Lukacs; Andreas Brech; Harald Stenmark |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2006-03-22 |
Journal Detail:
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Title: Molecular biology of the cell Volume: 17 ISSN: 1059-1524 ISO Abbreviation: Mol. Biol. Cell Publication Date: 2006 Jun |
Date Detail:
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Created Date: 2006-05-29 Completed Date: 2006-08-22 Revised Date: 2011-10-28 |
Medline Journal Info:
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Nlm Unique ID: 9201390 Medline TA: Mol Biol Cell Country: United States |
Other Details:
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Languages: eng Pagination: 2513-23 Citation Subset: IM |
Affiliation:
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Department of Biochemistry, Institute for Cancer Research, Norwegian Radium Hospital, Montebello, N-0310 Oslo, Norway. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Down-Regulation Endocytosis Endosomal Sorting Complexes Required for Transport Endosomes / metabolism, ultrastructure Gene Silencing Hela Cells Humans Lysosomes / metabolism Protein Subunits / metabolism RNA, Small Interfering / genetics Receptor, Epidermal Growth Factor / genetics, metabolism* Vesicular Transport Proteins / metabolism* |
| Chemical | |
Reg. No./Substance:
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0/CHMP3 protein, human; 0/Endosomal Sorting Complexes Required for Transport; 0/Protein Subunits; 0/RNA, Small Interfering; 0/Vesicular Transport Proteins; EC 2.7.10.1/Receptor, Epidermal Growth Factor |
| Comments/Corrections | |
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