DDB_G0289497 - dictyBase/community-annotations GitHub Wiki

DDB_G0289497 has been alleged to be a member of the dickkopf family (Guder et al, 2006). Mammals have four dickkopf genes (Dkk1, Dkk2, Dkk3 and Dkk4), of which Dkk1, 2 and 4 have been shown to be secreted antagonists of wingless signaling. Heterologous expression of any of these in vertebrate embryos leads to a reduction of posterior structures with accompanying enhancement of the head; hence the name dickkopf, which literally means fathead in German (Glinka et al, 1998).

The Dictyostelium gene is most similar to Dkk3, which is somewhat divergent from the others (see Niehrs, 2006). Members of the Dkk3 subfamily have signal peptides (as does DDB_G0289497) and are probably secreted proteins. Their interaction with wingless, however, is not as clearly established. Dkk3 fails to block the induction of secondary axes in Xenopus by wnts (Krupnik et al, 1999) but epigenetic silencing of Dkk3 has been implicated in the activation of beta-catenin signaling in lung cancer (Yue et al, 2008). The Dkk3 knockout mouse is viable and fertile, shows no major alterations in organ morphology or function, and has no enhanced propensity to develop tumors (del Barco Barrantes et al, 2006).

References

  • del Barco Barrantes et al (2006). Generation and characterization of dickkopf3 mutant mice. Molecular and Cellular Biology 26, 2317-2326.

  • Glinka et al (1998). Dickkopf-1 is a member of a new family of secreted proteins and functions in head induction. Nature 391, 357-362

  • Guder et al (2006). An ancient Wnt-Dickkopf antagonism in Hydra. Development 133, 901-911

  • Krupnik et al (1999) Functional and structural diversity of the human Dickkopf gene family. Gene 238, 301-313)

  • Niehrs (2006). Function and biological roles of the Dickkopf family of Wnt modulators. Oncogene 25, 7469-7481

  • Yue et al (2008) Downregulation of Dkk3 activatates beta-catenin/TCF-4 signaling in lung cancer. Carcinogenesis 29, 84-92

June 2008 Harry MacWilliams

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