Tankyrases maintain homeostasis of intestinal epithelium by preventing cell death.

ABSTRACT: Lgr5+ intestinal stem cells are crucial for fast homeostatic renewal of intestinal epithelium and Wnt/β-catenin signaling plays an essential role in this process by sustaining stem cell self-renewal. The poly(ADP-ribose) polymerases tankyrases (TNKSs) mediate protein poly-ADP-ribosylation and are involved in multiple cellular processes such as Wnt signaling regulation, mitotic progression and telomere maintenance. However, little is known about the physiological function of TNKSs in epithelium homeostasis regulation. Here, using Villin-creERT2;Tnks1-/-;Tnks2fl/fl (DKO) mice, we observed that loss of TNKSs causes a rapid decrease of Lgr5+ intestinal stem cells and magnified apoptosis in small intestinal crypts, leading to intestine degeneration and increased mouse mortality. Consistently, d

SUBMITTER: Ye P 

PROVIDER: S-EPMC6177203 | biostudies-literature | 2018 Sep

REPOSITORIES: biostudies-literature