The mutant p53-ID4 complex controls VEGFA isoforms by recruiting lncRNA MALAT1
The abundant, nuclear-retained, metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) has been associated with a poorly differentiated and aggressive phenotype of mammary carcinomas. This long non-coding RNA (lncRNA) localizes to nuclear speckles, where it interacts with a subset of spl...
| Main Authors: | , , , , , , , , , , , , , |
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| Format: | Article |
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Nature Publishing Group
2017
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| Online Access: | https://eprints.nottingham.ac.uk/43030/ |
| _version_ | 1848796627044663296 |
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| author | Pruszko, Magdalena Milano, Elisa Forcato, Mattia Donzelli, S. Ganci, Federica Di Agostino, Silvia De Panfilis, Simone Fazi, Francesco Bates, David O. Bicciato, Silvio Zylicz, Maciej Żylicz, Alicja Blandino, Giovanni Fontemaggi, Giulia |
| author_facet | Pruszko, Magdalena Milano, Elisa Forcato, Mattia Donzelli, S. Ganci, Federica Di Agostino, Silvia De Panfilis, Simone Fazi, Francesco Bates, David O. Bicciato, Silvio Zylicz, Maciej Żylicz, Alicja Blandino, Giovanni Fontemaggi, Giulia |
| author_sort | Pruszko, Magdalena |
| building | Nottingham Research Data Repository |
| collection | Online Access |
| description | The abundant, nuclear-retained, metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) has been associated with a poorly differentiated and aggressive phenotype of mammary carcinomas. This long non-coding RNA (lncRNA) localizes to nuclear speckles, where it interacts with a subset of splicing factors and modulates their activity. In this study, we demonstrate that oncogenic splicing factor SRSF1 bridges MALAT1 to mutant p53 and ID4 proteins in breast cancer cells. Mutant p53 and ID4 delocalize MALAT1 from nuclear speckles and favor its association with chromatin. This enables aberrant recruitment of MALAT1 on VEGFA pre-mRNA and modulation of VEGFA isoforms expression. Interestingly, VEGFA-dependent expression signatures associate with ID4 expression specifically in basal-like breast cancers carrying TP53 mutations. Our results highlight the key role for MALAT1 in control of VEGFA isoforms expression in breast cancer cells expressing gain-of-function mutant p53 and ID4 proteins. |
| first_indexed | 2025-11-14T19:50:59Z |
| format | Article |
| id | nottingham-43030 |
| institution | University of Nottingham Malaysia Campus |
| institution_category | Local University |
| last_indexed | 2025-11-14T19:50:59Z |
| publishDate | 2017 |
| publisher | Nature Publishing Group |
| recordtype | eprints |
| repository_type | Digital Repository |
| spelling | nottingham-430302020-05-04T18:51:56Z https://eprints.nottingham.ac.uk/43030/ The mutant p53-ID4 complex controls VEGFA isoforms by recruiting lncRNA MALAT1 Pruszko, Magdalena Milano, Elisa Forcato, Mattia Donzelli, S. Ganci, Federica Di Agostino, Silvia De Panfilis, Simone Fazi, Francesco Bates, David O. Bicciato, Silvio Zylicz, Maciej Żylicz, Alicja Blandino, Giovanni Fontemaggi, Giulia The abundant, nuclear-retained, metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) has been associated with a poorly differentiated and aggressive phenotype of mammary carcinomas. This long non-coding RNA (lncRNA) localizes to nuclear speckles, where it interacts with a subset of splicing factors and modulates their activity. In this study, we demonstrate that oncogenic splicing factor SRSF1 bridges MALAT1 to mutant p53 and ID4 proteins in breast cancer cells. Mutant p53 and ID4 delocalize MALAT1 from nuclear speckles and favor its association with chromatin. This enables aberrant recruitment of MALAT1 on VEGFA pre-mRNA and modulation of VEGFA isoforms expression. Interestingly, VEGFA-dependent expression signatures associate with ID4 expression specifically in basal-like breast cancers carrying TP53 mutations. Our results highlight the key role for MALAT1 in control of VEGFA isoforms expression in breast cancer cells expressing gain-of-function mutant p53 and ID4 proteins. Nature Publishing Group 2017-06-26 Article PeerReviewed Pruszko, Magdalena, Milano, Elisa, Forcato, Mattia, Donzelli, S., Ganci, Federica, Di Agostino, Silvia, De Panfilis, Simone, Fazi, Francesco, Bates, David O., Bicciato, Silvio, Zylicz, Maciej, Żylicz, Alicja, Blandino, Giovanni and Fontemaggi, Giulia (2017) The mutant p53-ID4 complex controls VEGFA isoforms by recruiting lncRNA MALAT1. EMBO Reports . e201643370. ISSN 1469-3178 lncRNA MALAT1 ASF/SF2 SRSF1 ID4 mutant p53 VEGFAxxxb VEGFA http://embor.embopress.org/content/early/2017/06/26/embr.201643370 doi:10.15252/embr.201643370 doi:10.15252/embr.201643370 |
| spellingShingle | lncRNA MALAT1 ASF/SF2 SRSF1 ID4 mutant p53 VEGFAxxxb VEGFA Pruszko, Magdalena Milano, Elisa Forcato, Mattia Donzelli, S. Ganci, Federica Di Agostino, Silvia De Panfilis, Simone Fazi, Francesco Bates, David O. Bicciato, Silvio Zylicz, Maciej Żylicz, Alicja Blandino, Giovanni Fontemaggi, Giulia The mutant p53-ID4 complex controls VEGFA isoforms by recruiting lncRNA MALAT1 |
| title | The mutant p53-ID4 complex controls VEGFA isoforms by recruiting lncRNA MALAT1 |
| title_full | The mutant p53-ID4 complex controls VEGFA isoforms by recruiting lncRNA MALAT1 |
| title_fullStr | The mutant p53-ID4 complex controls VEGFA isoforms by recruiting lncRNA MALAT1 |
| title_full_unstemmed | The mutant p53-ID4 complex controls VEGFA isoforms by recruiting lncRNA MALAT1 |
| title_short | The mutant p53-ID4 complex controls VEGFA isoforms by recruiting lncRNA MALAT1 |
| title_sort | mutant p53-id4 complex controls vegfa isoforms by recruiting lncrna malat1 |
| topic | lncRNA MALAT1 ASF/SF2 SRSF1 ID4 mutant p53 VEGFAxxxb VEGFA |
| url | https://eprints.nottingham.ac.uk/43030/ https://eprints.nottingham.ac.uk/43030/ https://eprints.nottingham.ac.uk/43030/ |