| First Author | Simeonova I | Year | 2013 |
| Journal | Cell Rep | Volume | 3 |
| Issue | 6 | Pages | 2046-58 |
| PubMed ID | 23770245 | Mgi Jnum | J:199308 |
| Mgi Id | MGI:5502258 | Doi | 10.1016/j.celrep.2013.05.028 |
| Citation | Simeonova I, et al. (2013) Mutant Mice Lacking the p53 C-Terminal Domain Model Telomere Syndromes. Cell Rep 3(6):2046-58 |
| abstractText | Mutations in p53, although frequent in human cancers, have not been implicated in telomere-related syndromes. Here, we show that homozygous mutant mice expressing p53(Delta31), a p53 lacking the C-terminal domain, exhibit increased p53 activity and suffer from aplastic anemia and pulmonary fibrosis, hallmarks of syndromes caused by short telomeres. Indeed, p53(Delta31/Delta31) mice had short telomeres and other phenotypic traits associated with the telomere disease dyskeratosis congenita and its severe variant the Hoyeraal-Hreidarsson syndrome. Heterozygous p53(+/Delta31) mice were only mildly affected, but decreased levels of Mdm4, a negative regulator of p53, led to a dramatic aggravation of their symptoms. Importantly, several genes involved in telomere metabolism were downregulated in p53(Delta31/Delta31) cells, including Dyskerin, Rtel1, and Tinf2, which are mutated in dyskeratosis congenita, and Terf1, which is implicated in aplastic anemia. Together, these data reveal that a truncating mutation can activate p53 and that p53 plays a major role in the regulation of telomere metabolism. |
