| First Author | La Torre M | Year | 2018 |
| Journal | Aging Cell | Volume | 17 |
| Issue | 4 | Pages | e12730 |
| PubMed ID | 29635765 | Mgi Jnum | J:276210 |
| Mgi Id | MGI:6315437 | Doi | 10.1111/acel.12730 |
| Citation | La Torre M, et al. (2018) Mice with reduced expression of the telomere-associated protein Ft1 develop p53-sensitive progeroid traits. Aging Cell 17(4):e12730 |
| abstractText | Human AKTIP and mouse Ft1 are orthologous ubiquitin E2 variant proteins involved in telomere maintenance and DNA replication. AKTIP also interacts with A- and B-type lamins. These features suggest that Ft1 may be implicated in aging regulatory pathways. Here, we show that cells derived from hypomorph Ft1 mutant (Ft1(kof/kof) ) mice exhibit telomeric defects and that Ft1(kof/kof) animals develop progeroid traits, including impaired growth, skeletal and skin defects, abnormal heart tissue, and sterility. We also demonstrate a genetic interaction between Ft1 and p53. The analysis of mice carrying mutations in both Ft1 and p53 (Ft1(kof/kof) ; p53(ko/ko) and Ft1(kof/kof) ; p53(+/ko) ) showed that reduction in p53 rescues the progeroid traits of Ft1 mutants, suggesting that they are at least in part caused by a p53-dependent DNA damage response. Conversely, Ft1 reduction alters lymphomagenesis in p53 mutant mice. These results identify Ft1 as a new player in the aging process and open the way to the analysis of its interactions with other progeria genes using the mouse model. |
