The Wnt antagonist Dickkopf-1 is regulated by Bmp signaling and c-Jun and modulates programmed cell death
- PMID: 11867524
- PMCID: PMC125884
- DOI: 10.1093/emboj/21.5.966
The Wnt antagonist Dickkopf-1 is regulated by Bmp signaling and c-Jun and modulates programmed cell death
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.
Figures







References
-
- Adachi-Yamada T., Fujimura-Kamada,K., Nishida,Y. and Matsumoto,K. (1999) Distortion of proximodistal information causes JNK-dependent apoptosis in Drosophila wing. Nature, 400, 166–169. - PubMed
-
- Angel P., Hattori,K., Smeal,T. and Karin,M. (1988) The jun proto-oncogene is positively autoregulated by its product, Jun/AP1. Cell, 55, 875–885. - PubMed
-
- Behrens A., Sibilia,M. and Wagner,E.F. (1999) Amino-terminal phosphorylation of c-Jun regulates stress-induced apoptosis and cellular proliferation. Nature Genet., 21, 326–329. - PubMed
-
- Bejsovec A. (2000) Wnt signaling: an embarrassment of receptors. Curr. Biol., 10, R919–R922. - PubMed
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources