Abstract

Apaf1 is a key regulator of the mitochondrial intrinsic pathway of apoptosis, as it activates executioner caspases by forming the apoptotic machinery apoptosome. Its genetic regulation and its post-translational modification are crucial under the various conditions where apoptosis occurs. Here we describe Ku70/86, a mediator of non-homologous end-joining pathway of DNA repair, as a novel regulator of Apaf1 transcription. Through analysing different Apaf1 promoter mutants, we identified an element repressing the Apaf1 promoter. We demonstrated that Ku70/86 is a nuclear factor able to bind this repressing element and downregulating Apaf1 transcription. We also found that Ku70/86 interaction with Apaf1 promoter is dynamically modulated upon DNA damage. The effect of this binding is a downregulation of Apaf1 expression immediately following the damage to DNA; conversely, we observed Apaf1 upregulation and apoptosis activation when Ku70/86 unleashes the Apaf1-repressing element. Therefore, besides regulating DNA repair, our results suggest that Ku70/86 binds to the Apaf1 promoter and represses its activity. This may help to inhibit the apoptosome pathway of cell death and contribute to regulate cell survival.

Autore Pugliese

• Fimia Gian Maria

Tutti gli autori

• De Zio D. , Bordi M. , Tino E. , Lanzuolo C. , Ferraro E. , Mora E. , Ciccosanti F. , Fimia G. M. , Orlando V. , Cecconi F.

Titolo volume/Rivista

CELL DEATH AND DIFFERENTIATION

Anno di pubblicazione

2011

ISSN

1476-5403

ISBN

Non Disponibile

Numero di citazioni Wos

13

Ultimo Aggiornamento Citazioni

25/04/2018

Numero di citazioni Scopus

13

Ultimo Aggiornamento Citazioni

26/04/2018

Settori ERC

Non Disponibile

Codici ASJC

Non Disponibile