Dataset Information

PAF and EZH2 induce Wnt/?-catenin signaling hyperactivation.

ABSTRACT: Fine control of Wnt signaling is essential for various cellular and developmental decision-making processes. However, deregulation of Wnt signaling leads to pathological consequences, one of which is cancer. Here, we identify a function of PAF, a component of translesion DNA synthesis, in modulating Wnt signaling. PAF is specifically overexpressed in colon cancer cells and intestinal stem cells and is required for colon cancer cell proliferation. In Xenopus laevis, ventrovegetal expression of PAF hyperactivates Wnt signaling, developing a secondary axis with ?-catenin target gene upregulation. Upon Wnt signaling activation, PAF dissociates from PCNA and binds directly to ?-catenin. Then, PAF recruits EZH2 to the ?-catenin transcriptional complex and specifically enhances Wnt target gene transactivation, independently of EZH2's methyltransferase activity. In mice, conditional expression of PAF induces intestinal neoplasia via Wnt signaling hyperactivation. Our studies reveal an unexpected role of PAF in regulating Wnt signaling and propose a regulatory mechanism of Wnt signaling during tumorigenesis.

SUBMITTER: Jung HY

PROVIDER: S-EPMC4040269 | biostudies-literature | 2013 Oct

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

PAF and EZH2 induce Wnt/β-catenin signaling hyperactivation.

Jung Hae-Yun HY Jun Sohee S Lee Moonsup M Kim Han-Cheon HC Wang Xin X Ji Hong H McCrea Pierre D PD Park Jae-Il JI

Molecular cell 20130919 2

Fine control of Wnt signaling is essential for various cellular and developmental decision-making processes. However, deregulation of Wnt signaling leads to pathological consequences, one of which is cancer. Here, we identify a function of PAF, a component of translesion DNA synthesis, in modulating Wnt signaling. PAF is specifically overexpressed in colon cancer cells and intestinal stem cells and is required for colon cancer cell proliferation. In Xenopus laevis, ventrovegetal expression of PA ...[more]

PMID: 24055345

Similar Datasets

Project description:Osteoarthritis (OA) is an autoimmune disease associated with increasing age. Typically, chondrocyte senescence is believed to serve an important role in the development and progression of OA. However, the specific mechanisms underlying chondrocyte senescence have not been fully addressed. The present study hypothesized that the Wnt/β-catenin signaling may represent a major regulator of chondrocyte senescence. In addition, the acetylated levels of p53 and sirtuin-1 (SIRT-1) were examined as putative markers for chondrocyte senescence, since activation of p53 is considered an important step in the regulation of senescence. The Wnt/β-catenin signaling pathway was activated using LiCl and inhibited using the Wnt signaling pathway inhibitor, dickkopf-1 (DKK1) in order to evaluate the role of this pathway in the development of OA. Senescent cells were detected using the senescence-associated indicator acidic senescence-associated β-galactosidase (SA-β-gal). The effects of p53 and p16 on chondrocyte senescence were assessed via activation of Wnt/β-catenin signaling using Wnt-1. In addition, β-catenin was transfected into chondrocytes to induce activation of the Wnt/β-catenin signaling pathway. Finally, a rabbit model of OA was used to assess whether the observed effects on the Wnt/β-catenin signaling pathway and the induction of chondrocyte senescence were perpetuated. Activation of Wnt/β-catenin signaling increased the expression levels of SA-β-gal, p53, p16 and acetylated p53. Transfection of β-catenin in chondrocytes increased the expression levels of acetylated p53 and decreased the expression levels of SIRT-1, which in turn deacetylated p53 and modulated its activity. Finally, the role of the Wnt/β-catenin signaling pathway was confirmed in the development of OA using a rabbit model with this condition. The present study suggested that activation of the Wnt/β-catenin signaling pathway promoted chondrocyte senescence, through downregulation of SIRT-1 and increased the expression of acetylated p53.

Dataset Information

PAF and EZH2 induce Wnt/?-catenin signaling hyperactivation.

Publications

PAF and EZH2 induce Wnt/β-catenin signaling hyperactivation.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets