E2F1 and E2F2 prevent replicative stress and subsequent p53-dependent organ involution.

ABSTRACT: Tissue homeostasis requires tight regulation of cellular proliferation, differentiation and apoptosis. E2F1 and E2F2 transcription factors share a critical role in tissue homeostasis, since their combined inactivation results in overall organ involution, specially affecting the pancreatic gland, which subsequently triggers diabetes. We have examined the mechanism by which these E2Fs regulate tissue homeostasis. We show that pancreas atrophy in E2F1/E2F2 double-knockout (DKO) mice is associated with mitochondrial apoptosis and activation of the p53 pathway in young animals, before the development of diabetes. A deregulated expression of E2F target genes was detected in pancreatic cells of young DKO animals, along with unscheduled DNA replication and activation of a DNA damage response. Impo

SUBMITTER: Iglesias-Ara A 

PROVIDER: S-EPMC4563787 | biostudies-literature | 2015 Oct

REPOSITORIES: biostudies-literature