Phosphorylation of ETS1 by Src Family Kinases Prevents Its Recognition by the COP1 Tumor Suppressor
Oncoproteins and tumor suppressors antagonistically converge on critical nodes governing neoplastic growth, invasion, and metastasis. We discovered that phosphorylation of the ETS1 and ETS2 transcriptional oncoproteins at specific serine or threonine residues creates binding sites for the COP1 tumor...
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| Format: | Article |
| Language: | en_US |
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Elsevier
2016
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| Online Access: | http://hdl.handle.net/1721.1/105867 https://orcid.org/0000-0002-9547-3251 https://orcid.org/0000-0001-7963-402X |
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| author | Lu, Gang Zhang, Qing Huang, Ying Song, Jiaxi Lim, Elgene Liu, Wenbin Bronson, Roderick T. Bowden, Michaela Brock, Jane Krop, Ian E. Dillon, Deborah A. Gygi, Steven P. Mills, Gordon B. Richardson, Andrea L. Signoretti, Sabina Kaelin, William G. Tomaino, Ross Yaffe, Michael B Ehrenberger, Tobias |
| author2 | Massachusetts Institute of Technology. Department of Biological Engineering |
| author_facet | Massachusetts Institute of Technology. Department of Biological Engineering Lu, Gang Zhang, Qing Huang, Ying Song, Jiaxi Lim, Elgene Liu, Wenbin Bronson, Roderick T. Bowden, Michaela Brock, Jane Krop, Ian E. Dillon, Deborah A. Gygi, Steven P. Mills, Gordon B. Richardson, Andrea L. Signoretti, Sabina Kaelin, William G. Tomaino, Ross Yaffe, Michael B Ehrenberger, Tobias |
| author_sort | Lu, Gang |
| collection | MIT |
| description | Oncoproteins and tumor suppressors antagonistically converge on critical nodes governing neoplastic growth, invasion, and metastasis. We discovered that phosphorylation of the ETS1 and ETS2 transcriptional oncoproteins at specific serine or threonine residues creates binding sites for the COP1 tumor suppressor protein, which is an ubiquitin ligase component, leading to their destruction. In the case of ETS1, however, phosphorylation of a neighboring tyrosine residue by Src family kinases disrupts COP1 binding, thereby stabilizing ETS1. Src-dependent accumulation of ETS1 in breast cancer cells promotes anchorage-independent growth in vitro and tumor growth in vivo. These findings expand the list of potential COP1 substrates to include proteins whose COP1-binding sites are subject to regulatory phosphorylation and provide insights into transformation by Src family kinases. |
| first_indexed | 2024-09-23T14:53:22Z |
| format | Article |
| id | mit-1721.1/105867 |
| institution | Massachusetts Institute of Technology |
| language | en_US |
| last_indexed | 2024-09-23T14:53:22Z |
| publishDate | 2016 |
| publisher | Elsevier |
| record_format | dspace |
| spelling | mit-1721.1/1058672022-10-01T23:13:23Z Phosphorylation of ETS1 by Src Family Kinases Prevents Its Recognition by the COP1 Tumor Suppressor Lu, Gang Zhang, Qing Huang, Ying Song, Jiaxi Lim, Elgene Liu, Wenbin Bronson, Roderick T. Bowden, Michaela Brock, Jane Krop, Ian E. Dillon, Deborah A. Gygi, Steven P. Mills, Gordon B. Richardson, Andrea L. Signoretti, Sabina Kaelin, William G. Tomaino, Ross Yaffe, Michael B Ehrenberger, Tobias Massachusetts Institute of Technology. Department of Biological Engineering Massachusetts Institute of Technology. Department of Biology Koch Institute for Integrative Cancer Research at MIT Yaffe, Michael B Ehrenberger, Tobias Oncoproteins and tumor suppressors antagonistically converge on critical nodes governing neoplastic growth, invasion, and metastasis. We discovered that phosphorylation of the ETS1 and ETS2 transcriptional oncoproteins at specific serine or threonine residues creates binding sites for the COP1 tumor suppressor protein, which is an ubiquitin ligase component, leading to their destruction. In the case of ETS1, however, phosphorylation of a neighboring tyrosine residue by Src family kinases disrupts COP1 binding, thereby stabilizing ETS1. Src-dependent accumulation of ETS1 in breast cancer cells promotes anchorage-independent growth in vitro and tumor growth in vivo. These findings expand the list of potential COP1 substrates to include proteins whose COP1-binding sites are subject to regulatory phosphorylation and provide insights into transformation by Src family kinases. 2016-12-19T15:13:23Z 2016-12-19T15:13:23Z 2014-08 2014-05 Article http://purl.org/eprint/type/JournalArticle 15356108 http://hdl.handle.net/1721.1/105867 Lu, Gang et al. “Phosphorylation of ETS1 by Src Family Kinases Prevents Its Recognition by the COP1 Tumor Suppressor.” Cancer Cell 26.2 (2014): 222–234. https://orcid.org/0000-0002-9547-3251 https://orcid.org/0000-0001-7963-402X en_US http://dx.doi.org/10.1016/j.ccr.2014.06.026 Cancer Cell Creative Commons Attribution-NonCommercial-NoDerivs License http://creativecommons.org/licenses/by-nc-nd/4.0/ application/pdf Elsevier PMC |
| spellingShingle | Lu, Gang Zhang, Qing Huang, Ying Song, Jiaxi Lim, Elgene Liu, Wenbin Bronson, Roderick T. Bowden, Michaela Brock, Jane Krop, Ian E. Dillon, Deborah A. Gygi, Steven P. Mills, Gordon B. Richardson, Andrea L. Signoretti, Sabina Kaelin, William G. Tomaino, Ross Yaffe, Michael B Ehrenberger, Tobias Phosphorylation of ETS1 by Src Family Kinases Prevents Its Recognition by the COP1 Tumor Suppressor |
| title | Phosphorylation of ETS1 by Src Family Kinases Prevents Its Recognition by the COP1 Tumor Suppressor |
| title_full | Phosphorylation of ETS1 by Src Family Kinases Prevents Its Recognition by the COP1 Tumor Suppressor |
| title_fullStr | Phosphorylation of ETS1 by Src Family Kinases Prevents Its Recognition by the COP1 Tumor Suppressor |
| title_full_unstemmed | Phosphorylation of ETS1 by Src Family Kinases Prevents Its Recognition by the COP1 Tumor Suppressor |
| title_short | Phosphorylation of ETS1 by Src Family Kinases Prevents Its Recognition by the COP1 Tumor Suppressor |
| title_sort | phosphorylation of ets1 by src family kinases prevents its recognition by the cop1 tumor suppressor |
| url | http://hdl.handle.net/1721.1/105867 https://orcid.org/0000-0002-9547-3251 https://orcid.org/0000-0001-7963-402X |
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