[HTML][HTML] The Wnt antagonist Dickkopf‐1 is regulated by Bmp signaling and c‐Jun and modulates programmed cell death

L Grotewold, U Rüther - The EMBO journal, 2002 - embopress.org
L Grotewold, U Rüther
The EMBO journal, 2002embopress.org
Abstract Dickkopf‐1 (Dkk‐1) has been shown to be a potent inhibitor of Wnt/β‐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 …
Abstract
Dickkopf‐1 (Dkk‐1) has been shown to be a potent inhibitor of Wnt/β‐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/β‐catenin signaling in response to different stress signals that all converge on the activation of c‐Jun in vivo.
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