E2F-1 regulation by an unusual DNA damage-responsive DP partner subunit.
E2F activity is negatively regulated by retinoblastoma protein (pRb) through binding to the E2F-1 subunit. Within the E2F heterodimer, DP proteins are E2F partner subunits that allow proper cell cycle progression. In contrast to the other DP proteins, the newest member of the family, DP-4, downregul...
| Main Authors: | , , , |
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| 格式: | Journal article |
| 語言: | English |
| 出版: |
2011
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| _version_ | 1826288255171035136 |
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| author | Ingram, L Munro, S Coutts, A La Thangue, N |
| author_facet | Ingram, L Munro, S Coutts, A La Thangue, N |
| author_sort | Ingram, L |
| collection | OXFORD |
| description | E2F activity is negatively regulated by retinoblastoma protein (pRb) through binding to the E2F-1 subunit. Within the E2F heterodimer, DP proteins are E2F partner subunits that allow proper cell cycle progression. In contrast to the other DP proteins, the newest member of the family, DP-4, downregulates E2F activity. In this study we report an unexpected role for DP-4 in regulating E2F-1 activity during the DNA damage response. Specifically, DP-4 is induced in DNA-damaged cells, upon which it binds to E2F-1 as a non-DNA-binding E2F-1/DP-4 complex. Consequently, depleting DP-4 in cells re-instates E2F-1 activity that coincides with increased levels of chromatin-bound E2F-1, E2F-1 target gene expression and associated apoptosis. Mutational analysis of DP-4 highlighted a C-terminal region, outside the DNA-binding domain, required for the negative control of E2F-1 activity. Our results define a new pathway, which acts independently of pRb and through a biochemically distinct mechanism, involved in negative regulation of E2F-1 activity. |
| first_indexed | 2024-03-07T02:10:57Z |
| format | Journal article |
| id | oxford-uuid:a09ecf81-9b71-4b9e-b067-f354c4735a7f |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T02:10:57Z |
| publishDate | 2011 |
| record_format | dspace |
| spelling | oxford-uuid:a09ecf81-9b71-4b9e-b067-f354c4735a7f2022-03-27T02:06:48ZE2F-1 regulation by an unusual DNA damage-responsive DP partner subunit.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:a09ecf81-9b71-4b9e-b067-f354c4735a7fEnglishSymplectic Elements at Oxford2011Ingram, LMunro, SCoutts, ALa Thangue, NE2F activity is negatively regulated by retinoblastoma protein (pRb) through binding to the E2F-1 subunit. Within the E2F heterodimer, DP proteins are E2F partner subunits that allow proper cell cycle progression. In contrast to the other DP proteins, the newest member of the family, DP-4, downregulates E2F activity. In this study we report an unexpected role for DP-4 in regulating E2F-1 activity during the DNA damage response. Specifically, DP-4 is induced in DNA-damaged cells, upon which it binds to E2F-1 as a non-DNA-binding E2F-1/DP-4 complex. Consequently, depleting DP-4 in cells re-instates E2F-1 activity that coincides with increased levels of chromatin-bound E2F-1, E2F-1 target gene expression and associated apoptosis. Mutational analysis of DP-4 highlighted a C-terminal region, outside the DNA-binding domain, required for the negative control of E2F-1 activity. Our results define a new pathway, which acts independently of pRb and through a biochemically distinct mechanism, involved in negative regulation of E2F-1 activity. |
| spellingShingle | Ingram, L Munro, S Coutts, A La Thangue, N E2F-1 regulation by an unusual DNA damage-responsive DP partner subunit. |
| title | E2F-1 regulation by an unusual DNA damage-responsive DP partner subunit. |
| title_full | E2F-1 regulation by an unusual DNA damage-responsive DP partner subunit. |
| title_fullStr | E2F-1 regulation by an unusual DNA damage-responsive DP partner subunit. |
| title_full_unstemmed | E2F-1 regulation by an unusual DNA damage-responsive DP partner subunit. |
| title_short | E2F-1 regulation by an unusual DNA damage-responsive DP partner subunit. |
| title_sort | e2f 1 regulation by an unusual dna damage responsive dp partner subunit |
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