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.

Mice with reduced expression of the telomere-associated protein Ft1 develop p53-sensitive progeroid traits / LA TORRE, Mattia; Merigliano, Chiara; Burla, Romina; Mottini, Carla; Zanetti, Giorgia; DEL GIUDICE, Simona; Carcuro, Mariateresa; Ilaria, Virdia; Bucciarelli, Elisabetta; Isabella, Manni; RAMPIONI VINCIGUERRA, GIAN LUCA; Giulia, Piaggio; Riminucci, Mara; Ana, Cumano; Bartolazzi, Armando; Verni', Fiammetta; Silvia, Soddu; Gatti, Maurizio; Saggio, Isabella. - In: AGING CELL. - ISSN 1474-9726. - ELETTRONICO. - 17:4(2018). [10.1111/acel.12730]

Mice with reduced expression of the telomere-associated protein Ft1 develop p53-sensitive progeroid traits

LA TORRE, MATTIA;Chiara Merigliano;Romina Burla;MOTTINI, CARLA;ZANETTI, GIORGIA;DEL GIUDICE, SIMONA;CARCURO, MARIATERESA;BUCCIARELLI, elisabetta;RAMPIONI VINCIGUERRA, GIAN LUCA;Mara Riminucci;Armando Bartolazzi;Fiammetta Verni;Maurizio Gatti
;
Isabella Saggio
2018

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.
2018
AKTIP; DNA damage; aging; lamins; progeria; telomeres
01 Pubblicazione su rivista::01a Articolo in rivista
Mice with reduced expression of the telomere-associated protein Ft1 develop p53-sensitive progeroid traits / LA TORRE, Mattia; Merigliano, Chiara; Burla, Romina; Mottini, Carla; Zanetti, Giorgia; DEL GIUDICE, Simona; Carcuro, Mariateresa; Ilaria, Virdia; Bucciarelli, Elisabetta; Isabella, Manni; RAMPIONI VINCIGUERRA, GIAN LUCA; Giulia, Piaggio; Riminucci, Mara; Ana, Cumano; Bartolazzi, Armando; Verni', Fiammetta; Silvia, Soddu; Gatti, Maurizio; Saggio, Isabella. - In: AGING CELL. - ISSN 1474-9726. - ELETTRONICO. - 17:4(2018). [10.1111/acel.12730]
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11573/1090295
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