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Cdc48/p97 and Shp1/p47 regulate autophagosome biogenesis in concert with ubiquitin-like Atg8

The molecular details of the biogenesis of double-membraned autophagosomes are poorly understood. We identify the Saccharomyces cerevisiae AAA–adenosine triphosphatase Cdc48 and its substrate-recruiting cofactor Shp1/Ubx1 as novel components needed for autophagosome biogenesis. In mammals, the Cdc48...

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Detalles Bibliográficos
Autores principales: Krick, Roswitha, Bremer, Sebastian, Welter, Evelyn, Schlotterhose, Petra, Muehe, Yvonne, Eskelinen, Eeva-Liisa, Thumm, Michael
Formato: Texto
Lenguaje:English
Publicado: The Rockefeller University Press 2010
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3101598/
https://www.ncbi.nlm.nih.gov/pubmed/20855502
http://dx.doi.org/10.1083/jcb.201002075
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author Krick, Roswitha
Bremer, Sebastian
Welter, Evelyn
Schlotterhose, Petra
Muehe, Yvonne
Eskelinen, Eeva-Liisa
Thumm, Michael
author_facet Krick, Roswitha
Bremer, Sebastian
Welter, Evelyn
Schlotterhose, Petra
Muehe, Yvonne
Eskelinen, Eeva-Liisa
Thumm, Michael
author_sort Krick, Roswitha
collection PubMed
description The molecular details of the biogenesis of double-membraned autophagosomes are poorly understood. We identify the Saccharomyces cerevisiae AAA–adenosine triphosphatase Cdc48 and its substrate-recruiting cofactor Shp1/Ubx1 as novel components needed for autophagosome biogenesis. In mammals, the Cdc48 homologue p97/VCP and the Shp1 homologue p47 mediate Golgi reassembly by extracting an unknown monoubiquitinated fusion regulator from a complex. We find no requirement of ubiquitination or the proteasome system for autophagosome biogenesis but detect interaction of Shp1 with the ubiquitin-fold autophagy protein Atg8. Atg8 coupled to phosphatidylethanolamine (PE) is crucial for autophagosome elongation and, in vitro, mediates tethering and hemifusion. Interaction with Shp1 requires an FK motif within the N-terminal non–ubiquitin-like Atg8 domain. Based on our data, we speculate that autophagosome formation, in contrast to Golgi reassembly, requires a complex in which Atg8 functionally substitutes ubiquitin. This, for the first time, would give a rationale for use of the ubiquitin-like Atg8 during macroautophagy and would explain why Atg8-PE delipidation is necessary for efficient macroautophagy.
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spelling pubmed-31015982011-06-06 Cdc48/p97 and Shp1/p47 regulate autophagosome biogenesis in concert with ubiquitin-like Atg8 Krick, Roswitha Bremer, Sebastian Welter, Evelyn Schlotterhose, Petra Muehe, Yvonne Eskelinen, Eeva-Liisa Thumm, Michael J Cell Biol Research Articles The molecular details of the biogenesis of double-membraned autophagosomes are poorly understood. We identify the Saccharomyces cerevisiae AAA–adenosine triphosphatase Cdc48 and its substrate-recruiting cofactor Shp1/Ubx1 as novel components needed for autophagosome biogenesis. In mammals, the Cdc48 homologue p97/VCP and the Shp1 homologue p47 mediate Golgi reassembly by extracting an unknown monoubiquitinated fusion regulator from a complex. We find no requirement of ubiquitination or the proteasome system for autophagosome biogenesis but detect interaction of Shp1 with the ubiquitin-fold autophagy protein Atg8. Atg8 coupled to phosphatidylethanolamine (PE) is crucial for autophagosome elongation and, in vitro, mediates tethering and hemifusion. Interaction with Shp1 requires an FK motif within the N-terminal non–ubiquitin-like Atg8 domain. Based on our data, we speculate that autophagosome formation, in contrast to Golgi reassembly, requires a complex in which Atg8 functionally substitutes ubiquitin. This, for the first time, would give a rationale for use of the ubiquitin-like Atg8 during macroautophagy and would explain why Atg8-PE delipidation is necessary for efficient macroautophagy. The Rockefeller University Press 2010-09-20 /pmc/articles/PMC3101598/ /pubmed/20855502 http://dx.doi.org/10.1083/jcb.201002075 Text en © 2010 Krick et al. This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 3.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/3.0/).
spellingShingle Research Articles
Krick, Roswitha
Bremer, Sebastian
Welter, Evelyn
Schlotterhose, Petra
Muehe, Yvonne
Eskelinen, Eeva-Liisa
Thumm, Michael
Cdc48/p97 and Shp1/p47 regulate autophagosome biogenesis in concert with ubiquitin-like Atg8
title Cdc48/p97 and Shp1/p47 regulate autophagosome biogenesis in concert with ubiquitin-like Atg8
title_full Cdc48/p97 and Shp1/p47 regulate autophagosome biogenesis in concert with ubiquitin-like Atg8
title_fullStr Cdc48/p97 and Shp1/p47 regulate autophagosome biogenesis in concert with ubiquitin-like Atg8
title_full_unstemmed Cdc48/p97 and Shp1/p47 regulate autophagosome biogenesis in concert with ubiquitin-like Atg8
title_short Cdc48/p97 and Shp1/p47 regulate autophagosome biogenesis in concert with ubiquitin-like Atg8
title_sort cdc48/p97 and shp1/p47 regulate autophagosome biogenesis in concert with ubiquitin-like atg8
topic Research Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3101598/
https://www.ncbi.nlm.nih.gov/pubmed/20855502
http://dx.doi.org/10.1083/jcb.201002075
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