Requirement for phosphorylation of P53 at Ser312 in suppression of chemical carcinogenesis
The p53 tumour suppressor is activated in response to a wide variety of genotoxic stresses, frequently via post-translational modification. Using a knock in mouse model with a Ser312 to Ala mutation, we show here that phosphorylation of p53 on Ser312 helps to prevent tumour induction by the alkylati...
| Päätekijät: | , |
|---|---|
| Aineistotyyppi: | Journal article |
| Kieli: | English |
| Julkaistu: |
Springer Nature
2013
|
| _version_ | 1826258820533321728 |
|---|---|
| author | Slee, E Lu, X |
| author_facet | Slee, E Lu, X |
| author_sort | Slee, E |
| collection | OXFORD |
| description | The p53 tumour suppressor is activated in response to a wide variety of genotoxic stresses, frequently via post-translational modification. Using a knock in mouse model with a Ser312 to Ala mutation, we show here that phosphorylation of p53 on Ser312 helps to prevent tumour induction by the alkylating agent MNU, which predominantly caused T cell lymphomas. This is consistent with our previous observation that p53312A/A mice are more susceptible to X-ray induced tumourigenesis. Phosphorylation on Ser312 aids p53's interaction with E2F1 and enhances p53-mediated apoptosis. Loss of E2F1 alone does not affect tumour susceptibility to MNU, but its absence partially rescues tumour formation in p53312A/A mice, thus reflecting the oncogenic properties of E2F1. Our data confirms the participation of Ser312 phosphorylation in tumour suppression by p53. |
| first_indexed | 2024-03-06T18:40:02Z |
| format | Journal article |
| id | oxford-uuid:0c901b27-70f3-4580-8650-2ea0d7e9e34e |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-06T18:40:02Z |
| publishDate | 2013 |
| publisher | Springer Nature |
| record_format | dspace |
| spelling | oxford-uuid:0c901b27-70f3-4580-8650-2ea0d7e9e34e2022-03-26T09:35:43ZRequirement for phosphorylation of P53 at Ser312 in suppression of chemical carcinogenesisJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:0c901b27-70f3-4580-8650-2ea0d7e9e34eEnglishSymplectic Elements at OxfordSpringer Nature2013Slee, ELu, XThe p53 tumour suppressor is activated in response to a wide variety of genotoxic stresses, frequently via post-translational modification. Using a knock in mouse model with a Ser312 to Ala mutation, we show here that phosphorylation of p53 on Ser312 helps to prevent tumour induction by the alkylating agent MNU, which predominantly caused T cell lymphomas. This is consistent with our previous observation that p53312A/A mice are more susceptible to X-ray induced tumourigenesis. Phosphorylation on Ser312 aids p53's interaction with E2F1 and enhances p53-mediated apoptosis. Loss of E2F1 alone does not affect tumour susceptibility to MNU, but its absence partially rescues tumour formation in p53312A/A mice, thus reflecting the oncogenic properties of E2F1. Our data confirms the participation of Ser312 phosphorylation in tumour suppression by p53. |
| spellingShingle | Slee, E Lu, X Requirement for phosphorylation of P53 at Ser312 in suppression of chemical carcinogenesis |
| title | Requirement for phosphorylation of P53 at Ser312 in suppression of chemical carcinogenesis |
| title_full | Requirement for phosphorylation of P53 at Ser312 in suppression of chemical carcinogenesis |
| title_fullStr | Requirement for phosphorylation of P53 at Ser312 in suppression of chemical carcinogenesis |
| title_full_unstemmed | Requirement for phosphorylation of P53 at Ser312 in suppression of chemical carcinogenesis |
| title_short | Requirement for phosphorylation of P53 at Ser312 in suppression of chemical carcinogenesis |
| title_sort | requirement for phosphorylation of p53 at ser312 in suppression of chemical carcinogenesis |
| work_keys_str_mv | AT sleee requirementforphosphorylationofp53atser312insuppressionofchemicalcarcinogenesis AT lux requirementforphosphorylationofp53atser312insuppressionofchemicalcarcinogenesis |