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Disruption of Vps4 and JNK Function in Drosophila Causes Tumour Growth
Several regulators of endocytic trafficking have recently been identified as tumour suppressors in Drosophila. These include components of the endosomal sorting complex required for transport (ESCRT) machinery. Disruption of subunits of ESCRT-I and –II leads to cell-autonomous endosomal accumulation...
Autores principales: | , , , , , , , |
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Formato: | Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2009
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2632753/ https://www.ncbi.nlm.nih.gov/pubmed/19194501 http://dx.doi.org/10.1371/journal.pone.0004354 |
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author | Rodahl, Lina M. Haglund, Kaisa Sem-Jacobsen, Catherine Wendler, Franz Vincent, Jean-Paul Lindmo, Karine Rusten, Tor Erik Stenmark, Harald |
author_facet | Rodahl, Lina M. Haglund, Kaisa Sem-Jacobsen, Catherine Wendler, Franz Vincent, Jean-Paul Lindmo, Karine Rusten, Tor Erik Stenmark, Harald |
author_sort | Rodahl, Lina M. |
collection | PubMed |
description | Several regulators of endocytic trafficking have recently been identified as tumour suppressors in Drosophila. These include components of the endosomal sorting complex required for transport (ESCRT) machinery. Disruption of subunits of ESCRT-I and –II leads to cell-autonomous endosomal accumulation of ubiquitinated receptors, loss of apicobasal polarity and epithelial integrity, and increased cell death. Here we report that disruption of the ATPase dVps4, the most downstream component of the ESCRT machinery, causes the same array of cellular phenotypes. We find that loss of epithelial integrity and increased apoptosis, but not loss of cell polarity, require the activation of JNK signalling. Abrogation of JNK signalling prevents apoptosis in dVps4 deficient cells. Indeed double deficiency in dVps4 and JNK signalling leads to the formation of neoplastic tumours. We conclude that dvps4 is a tumour suppressor in Drosophila and that JNK is central to the cell-autonomous phenotypes of ESCRT-deficient cells. |
format | Text |
id | pubmed-2632753 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2009 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-26327532009-02-04 Disruption of Vps4 and JNK Function in Drosophila Causes Tumour Growth Rodahl, Lina M. Haglund, Kaisa Sem-Jacobsen, Catherine Wendler, Franz Vincent, Jean-Paul Lindmo, Karine Rusten, Tor Erik Stenmark, Harald PLoS One Research Article Several regulators of endocytic trafficking have recently been identified as tumour suppressors in Drosophila. These include components of the endosomal sorting complex required for transport (ESCRT) machinery. Disruption of subunits of ESCRT-I and –II leads to cell-autonomous endosomal accumulation of ubiquitinated receptors, loss of apicobasal polarity and epithelial integrity, and increased cell death. Here we report that disruption of the ATPase dVps4, the most downstream component of the ESCRT machinery, causes the same array of cellular phenotypes. We find that loss of epithelial integrity and increased apoptosis, but not loss of cell polarity, require the activation of JNK signalling. Abrogation of JNK signalling prevents apoptosis in dVps4 deficient cells. Indeed double deficiency in dVps4 and JNK signalling leads to the formation of neoplastic tumours. We conclude that dvps4 is a tumour suppressor in Drosophila and that JNK is central to the cell-autonomous phenotypes of ESCRT-deficient cells. Public Library of Science 2009-02-04 /pmc/articles/PMC2632753/ /pubmed/19194501 http://dx.doi.org/10.1371/journal.pone.0004354 Text en Rodahl et al. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited. |
spellingShingle | Research Article Rodahl, Lina M. Haglund, Kaisa Sem-Jacobsen, Catherine Wendler, Franz Vincent, Jean-Paul Lindmo, Karine Rusten, Tor Erik Stenmark, Harald Disruption of Vps4 and JNK Function in Drosophila Causes Tumour Growth |
title | Disruption of Vps4 and JNK Function in Drosophila Causes Tumour Growth |
title_full | Disruption of Vps4 and JNK Function in Drosophila Causes Tumour Growth |
title_fullStr | Disruption of Vps4 and JNK Function in Drosophila Causes Tumour Growth |
title_full_unstemmed | Disruption of Vps4 and JNK Function in Drosophila Causes Tumour Growth |
title_short | Disruption of Vps4 and JNK Function in Drosophila Causes Tumour Growth |
title_sort | disruption of vps4 and jnk function in drosophila causes tumour growth |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2632753/ https://www.ncbi.nlm.nih.gov/pubmed/19194501 http://dx.doi.org/10.1371/journal.pone.0004354 |
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