Mice with reduced expression of the telomere‐associated protein Ft1 develop p53‐sensitive progeroid traits |
| |
| Authors: | Mattia La Torre Chiara Merigliano Romina Burla Carla Mottini Giorgia Zanetti Simona Del Giudice Mariateresa Carcuro Ilaria Virdia Elisabetta Bucciarelli Isabella Manni Gianluca Rampioni Vinciguerra Giulia Piaggio Mara Riminucci Ana Cumano Armando Bartolazzi Fiammetta Vernì Silvia Soddu Maurizio Gatti Isabella Saggio |
| |
| Institution: | 1. Dipartimento di Biologia e Biotecnologie “C. Darwin”, Sapienza Università di Roma, Rome, Italy;2. Dipartimento di Ricerca, Diagnostica Avanzata e Innovazione Tecnologica, Istituto Nazionale Tumori Regina Elena, Rome, Italy;3. Istituto di Biologia e Patologia Molecolari del CNR, Rome, Italy;4. Azienda Ospedaliera Sant'Andrea, Rome, Italy;5. Dipartimento di Medicina Molecolare, Sapienza Università di Roma, Rome, Italy;6. Lymphopoiesis Unit, Institut Pasteur, Paris, France |
| |
| Abstract: | 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 (Ft1kof/kof) mice exhibit telomeric defects and that Ft1kof/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 (Ft1kof/kof; p53ko/ko and Ft1kof/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. |
| |
| Keywords: | aging AKTIP DNA damage lamins progeria telomeres |
|
|
