| First Author | Slatter TL | Year | 2015 |
| Journal | Cell Death Dis | Volume | 6 |
| Pages | e1783 | PubMed ID | 26068791 |
| Mgi Jnum | J:317526 | Mgi Id | MGI:6855984 |
| Doi | 10.1038/cddis.2015.149 | Citation | Slatter TL, et al. (2015) Delta122p53, a mouse model of Delta133p53alpha, enhances the tumor-suppressor activities of an attenuated p53 mutant. Cell Death Dis 6:e1783 |
| abstractText | Growing evidence suggests the Delta133p53alpha isoform may function as an oncogene. It is overexpressed in many tumors, stimulates pathways involved in tumor progression, and inhibits some activities of wild-type p53, including transactivation and apoptosis. We hypothesized that Delta133p53alpha would have an even more profound effect on p53 variants with weaker tumor-suppressor capability. We tested this using a mouse model heterozygous for a Delta133p53alpha-like isoform (Delta122p53) and a p53 mutant with weak tumor-suppressor function (mDeltapro). The Delta122p53/mDeltapro mice showed a unique survival curve with a wide range of survival times (92-495 days) which was much greater than mDeltapro/- mice (range 120-250 days) and mice heterozygous for the Delta122p53 and p53 null alleles (Delta122p53/-, range 78-150 days), suggesting Delta122p53 increased the tumor-suppressor activity of mDeltapro. Moreover, some of the mice that survived longest only developed benign tumors. In vitro analyses to investigate why some Delta122p53/mDeltapro mice were protected from aggressive tumors revealed that Delta122p53 stabilized mDeltapro and prolonged the response to DNA damage. Similar effects of Delta122p53 and Delta133p53alpha were observed on wild-type of full-length p53, but these did not result in improved biological responses. The data suggest that Delta122p53 (and Delta133p53alpha) could offer some protection against tumors by enhancing the p53 response to stress. |
