Phosphorylation of ASPP2 by RAS/MAPK pathway is critical for its full pro-apoptotic function
We reported recently that apoptosis-stimulating protein of p53 (ASPP) 2, an activator of p53, co-operates with oncogenic RAS to enhance the transcription and apoptotic function of p53. However, the detailed mechanism remains unknown. Here we show that ASPP2 is a novel substrate of mitogen-activated...
| Main Authors: | , , , |
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| Format: | Journal article |
| Language: | English |
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Public Library of Science
2013
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| _version_ | 1797099978625122304 |
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| author | Godin-Heymann, N Wang, Y Slee, E Lu, X |
| author_facet | Godin-Heymann, N Wang, Y Slee, E Lu, X |
| author_sort | Godin-Heymann, N |
| collection | OXFORD |
| description | We reported recently that apoptosis-stimulating protein of p53 (ASPP) 2, an activator of p53, co-operates with oncogenic RAS to enhance the transcription and apoptotic function of p53. However, the detailed mechanism remains unknown. Here we show that ASPP2 is a novel substrate of mitogen-activated protein kinase (MAPK). Phosphorylation of ASPP2 by MAPK is required for RAS-induced increased binding to p53 and increased transactivation of pro-apoptotic genes. In contrast, an ASPP2 phosphorylation mutant exhibits reduced p53 binding and fails to enhance transactivation and apoptosis. Thus phosphorylation of ASPP2 by RAS/MAPK pathway provides a novel link between RAS and p53 in regulating apoptosis. |
| first_indexed | 2024-03-07T05:31:12Z |
| format | Journal article |
| id | oxford-uuid:e256093d-e54f-42ea-bffb-ed9c9595c924 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T05:31:12Z |
| publishDate | 2013 |
| publisher | Public Library of Science |
| record_format | dspace |
| spelling | oxford-uuid:e256093d-e54f-42ea-bffb-ed9c9595c9242022-03-27T10:00:24ZPhosphorylation of ASPP2 by RAS/MAPK pathway is critical for its full pro-apoptotic functionJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:e256093d-e54f-42ea-bffb-ed9c9595c924EnglishSymplectic Elements at OxfordPublic Library of Science2013Godin-Heymann, NWang, YSlee, ELu, XWe reported recently that apoptosis-stimulating protein of p53 (ASPP) 2, an activator of p53, co-operates with oncogenic RAS to enhance the transcription and apoptotic function of p53. However, the detailed mechanism remains unknown. Here we show that ASPP2 is a novel substrate of mitogen-activated protein kinase (MAPK). Phosphorylation of ASPP2 by MAPK is required for RAS-induced increased binding to p53 and increased transactivation of pro-apoptotic genes. In contrast, an ASPP2 phosphorylation mutant exhibits reduced p53 binding and fails to enhance transactivation and apoptosis. Thus phosphorylation of ASPP2 by RAS/MAPK pathway provides a novel link between RAS and p53 in regulating apoptosis. |
| spellingShingle | Godin-Heymann, N Wang, Y Slee, E Lu, X Phosphorylation of ASPP2 by RAS/MAPK pathway is critical for its full pro-apoptotic function |
| title | Phosphorylation of ASPP2 by RAS/MAPK pathway is critical for its full pro-apoptotic function |
| title_full | Phosphorylation of ASPP2 by RAS/MAPK pathway is critical for its full pro-apoptotic function |
| title_fullStr | Phosphorylation of ASPP2 by RAS/MAPK pathway is critical for its full pro-apoptotic function |
| title_full_unstemmed | Phosphorylation of ASPP2 by RAS/MAPK pathway is critical for its full pro-apoptotic function |
| title_short | Phosphorylation of ASPP2 by RAS/MAPK pathway is critical for its full pro-apoptotic function |
| title_sort | phosphorylation of aspp2 by ras mapk pathway is critical for its full pro apoptotic function |
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