Mice with reduced expression of the telomere‐associated protein Ft1 develop p53‐sensitive progeroid traits. Issue 4 (10th April 2018)

• Record Type: Journal Article
• Authors: La Torre, Mattia; Merigliano, Chiara; Burla, Romina; Mottini, Carla; Zanetti, Giorgia; Del Giudice, Simona; Carcuro, Mariateresa; Virdia, Ilaria; Bucciarelli, Elisabetta; Manni, Isabella; Vinciguerra, Gianluca Rampioni; Piaggio, Giulia; Riminucci, Mara; Cumano, Ana; Bartolazzi, Armando; Vernì, Fiammetta; Soddu, Silvia; Gatti, Maurizio; Saggio, Isabella
• Is Part Of: Aging cell. Volume 17:Issue 4(2018)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2018-04-10
• Subjects: aging -- AKTIP -- DNA damage -- lamins -- progeria -- telomeres; Cells -- Aging -- Periodicals; 571.8783605
• DOI: 10.1111/acel.12730
• Languages: English
• ISSNs: 1474-9718

Abstract

Summary: 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.