Pleiotropic effect of somatic mutations in the E2F subunit DP-1 gene in human cancer
Transcription factor E2F-1 and its interaction with pRb provide a key point of control in cell proliferation. E2F-1 participates in both cell cycle progression and apoptosis, and in cells exists with a DP dimerization partner protein, the most prominent being DP-1. By mining the tumor tissue and can...
| Main Authors: | , , |
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| Format: | Journal article |
| Language: | English |
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Nature Publishing Group
2014
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| _version_ | 1797101251012329472 |
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| author | Munro, S Oppermann, U La Thangue, N |
| author_facet | Munro, S Oppermann, U La Thangue, N |
| author_sort | Munro, S |
| collection | OXFORD |
| description | Transcription factor E2F-1 and its interaction with pRb provide a key point of control in cell proliferation. E2F-1 participates in both cell cycle progression and apoptosis, and in cells exists with a DP dimerization partner protein, the most prominent being DP-1. By mining the tumor tissue and cancer cell line encyclopedia genomic databases, we identified the first somatic mutations in the DP-1 gene and describe 53 distinct mutation events here. The mutations are mostly missense mutations, but also include nonsense and frame-shift mutations that result in truncated DP-1 derivatives. Mutation occurs throughout the DP-1 gene but generally leaves protein dimerization activity intact. This allows the mutant derivatives to affect the properties of the E2F-1/DP-1 heterodimer through a transdominant mechanism, which changes the DNA binding, transcriptional activation and pRb-binding properties of the heterodimer. In particular, many DP-1 mutants were found to impair E2F-1-dependent apoptosis. Our results establish that somatic mutations in DP-1 uncouple normal control of the E2F pathway, and thus define a new mechanism that could contribute to aberrant proliferation in tumor cells. © 2014 Macmillan Publishers Limited. |
| first_indexed | 2024-03-07T05:49:10Z |
| format | Journal article |
| id | oxford-uuid:e84085a7-35cb-4e88-ba57-b31e1bf65f75 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T05:49:10Z |
| publishDate | 2014 |
| publisher | Nature Publishing Group |
| record_format | dspace |
| spelling | oxford-uuid:e84085a7-35cb-4e88-ba57-b31e1bf65f752022-03-27T10:45:20ZPleiotropic effect of somatic mutations in the E2F subunit DP-1 gene in human cancerJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:e84085a7-35cb-4e88-ba57-b31e1bf65f75EnglishSymplectic Elements at OxfordNature Publishing Group2014Munro, SOppermann, ULa Thangue, NTranscription factor E2F-1 and its interaction with pRb provide a key point of control in cell proliferation. E2F-1 participates in both cell cycle progression and apoptosis, and in cells exists with a DP dimerization partner protein, the most prominent being DP-1. By mining the tumor tissue and cancer cell line encyclopedia genomic databases, we identified the first somatic mutations in the DP-1 gene and describe 53 distinct mutation events here. The mutations are mostly missense mutations, but also include nonsense and frame-shift mutations that result in truncated DP-1 derivatives. Mutation occurs throughout the DP-1 gene but generally leaves protein dimerization activity intact. This allows the mutant derivatives to affect the properties of the E2F-1/DP-1 heterodimer through a transdominant mechanism, which changes the DNA binding, transcriptional activation and pRb-binding properties of the heterodimer. In particular, many DP-1 mutants were found to impair E2F-1-dependent apoptosis. Our results establish that somatic mutations in DP-1 uncouple normal control of the E2F pathway, and thus define a new mechanism that could contribute to aberrant proliferation in tumor cells. © 2014 Macmillan Publishers Limited. |
| spellingShingle | Munro, S Oppermann, U La Thangue, N Pleiotropic effect of somatic mutations in the E2F subunit DP-1 gene in human cancer |
| title | Pleiotropic effect of somatic mutations in the E2F subunit DP-1 gene in human cancer |
| title_full | Pleiotropic effect of somatic mutations in the E2F subunit DP-1 gene in human cancer |
| title_fullStr | Pleiotropic effect of somatic mutations in the E2F subunit DP-1 gene in human cancer |
| title_full_unstemmed | Pleiotropic effect of somatic mutations in the E2F subunit DP-1 gene in human cancer |
| title_short | Pleiotropic effect of somatic mutations in the E2F subunit DP-1 gene in human cancer |
| title_sort | pleiotropic effect of somatic mutations in the e2f subunit dp 1 gene in human cancer |
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