The Wnt Antagonist Dickkopf-1 is Regulated by Bmp Signaling and C-Jun and Modulates Programmed Cell Death

Overview

Journal EMBO J

Specialties Biotechnology
Molecular Biology

Date 2002 Feb 28

PMID 11867524

Citations 72

Authors

Lars Grotewold

Ulrich Ruther

Affiliations

Soon will be listed here.

Abstract

Dickkopf-1 (Dkk-1) has been shown to be a potent inhibitor of Wnt/beta-catenin signaling in a variety of assays and organisms. In this study, we show that expression of Dkk-1 overlaps significantly with the sites of programmed cell death in normal as well as mutant vertebrate limb development, and identify several of its upstream regulators, one of which is Bmp-4. Interestingly, Bmp-4 only activates Dkk-1 when it concomitantly induces apoptosis. Moreover, Dkk-1 is heavily up-regulated by UV irradiation and several other genotoxic stimuli. We further show that normal expression of Dkk-1 is dependent on the Ap-1 family member c-Jun and that overexpression of Dkk-1 enhances Bmp-triggered apoptosis in the vertebrate limb. Taken together, our results provide evidence for an important role of Dkk-1-mediated inhibition of Wnt/beta-catenin signaling in response to different stress signals that all converge on the activation of c-Jun in vivo.

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