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Siah2 regulates tight junction integrity and cell polarity through control of ASPP2 stability
Changes in cell adhesion and polarity are closely associated with epithelial cell transformation and metastatic capacity. The tumor suppressor protein ASPP2 has been implicated in control of cell adhesion and polarity, through its effect on the PAR complex. Here we demonstrate that under hypoxic con...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
2013
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3917971/ https://www.ncbi.nlm.nih.gov/pubmed/23644657 http://dx.doi.org/10.1038/onc.2013.149 |
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author | Kim, Hyungsoo Claps, Guisepinna Möller, Andreas Bowtell, David Lu, Xin Ronai, Ze'ev A. |
author_facet | Kim, Hyungsoo Claps, Guisepinna Möller, Andreas Bowtell, David Lu, Xin Ronai, Ze'ev A. |
author_sort | Kim, Hyungsoo |
collection | PubMed |
description | Changes in cell adhesion and polarity are closely associated with epithelial cell transformation and metastatic capacity. The tumor suppressor protein ASPP2 has been implicated in control of cell adhesion and polarity, through its effect on the PAR complex. Here we demonstrate that under hypoxic conditions the ubiquitin ligase Siah2 controls ASPP2 availability, with concomitant effect on epithelial cell polarity. LC-MS/MS analysis identified ASPP2 and ASPP1 as Siah2 interacting proteins. Biochemical analysis confirmed this interaction and mapped degron motifs within ASPP2, which are required for Siah2-mediated ubiquitination and proteasomal-dependent degradation. Inhibition of Siah2 expression increases ASPP2 levels and enhances ASPP2-dependent maintenance of TJ integrity and polarized architecture in 3D organotypic culture. Conversely, increase of Siah2 expression under hypoxia decreases ASPP2 levels and the formation of apical polarity in 3D culture. In all, our studies demonstrate the role of Siah2 in regulation of TJ integrity and cell polarity under hypoxia, through its regulation of ASPP2 stability. |
format | Online Article Text |
id | pubmed-3917971 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2013 |
record_format | MEDLINE/PubMed |
spelling | pubmed-39179712014-10-10 Siah2 regulates tight junction integrity and cell polarity through control of ASPP2 stability Kim, Hyungsoo Claps, Guisepinna Möller, Andreas Bowtell, David Lu, Xin Ronai, Ze'ev A. Oncogene Article Changes in cell adhesion and polarity are closely associated with epithelial cell transformation and metastatic capacity. The tumor suppressor protein ASPP2 has been implicated in control of cell adhesion and polarity, through its effect on the PAR complex. Here we demonstrate that under hypoxic conditions the ubiquitin ligase Siah2 controls ASPP2 availability, with concomitant effect on epithelial cell polarity. LC-MS/MS analysis identified ASPP2 and ASPP1 as Siah2 interacting proteins. Biochemical analysis confirmed this interaction and mapped degron motifs within ASPP2, which are required for Siah2-mediated ubiquitination and proteasomal-dependent degradation. Inhibition of Siah2 expression increases ASPP2 levels and enhances ASPP2-dependent maintenance of TJ integrity and polarized architecture in 3D organotypic culture. Conversely, increase of Siah2 expression under hypoxia decreases ASPP2 levels and the formation of apical polarity in 3D culture. In all, our studies demonstrate the role of Siah2 in regulation of TJ integrity and cell polarity under hypoxia, through its regulation of ASPP2 stability. 2013-05-06 2014-04-10 /pmc/articles/PMC3917971/ /pubmed/23644657 http://dx.doi.org/10.1038/onc.2013.149 Text en Users may view, print, copy, download and text and data- mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use: http://www.nature.com/authors/editorial_policies/license.html#terms |
spellingShingle | Article Kim, Hyungsoo Claps, Guisepinna Möller, Andreas Bowtell, David Lu, Xin Ronai, Ze'ev A. Siah2 regulates tight junction integrity and cell polarity through control of ASPP2 stability |
title | Siah2 regulates tight junction integrity and cell polarity through control of ASPP2 stability |
title_full | Siah2 regulates tight junction integrity and cell polarity through control of ASPP2 stability |
title_fullStr | Siah2 regulates tight junction integrity and cell polarity through control of ASPP2 stability |
title_full_unstemmed | Siah2 regulates tight junction integrity and cell polarity through control of ASPP2 stability |
title_short | Siah2 regulates tight junction integrity and cell polarity through control of ASPP2 stability |
title_sort | siah2 regulates tight junction integrity and cell polarity through control of aspp2 stability |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3917971/ https://www.ncbi.nlm.nih.gov/pubmed/23644657 http://dx.doi.org/10.1038/onc.2013.149 |
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