Scientific Publications by FDA Staff

Oncogene 2005 Dec 15;24(56):8229-39

Drosophila caliban, a nuclear export mediator, can function as a tumor suppressor in human lung cancer cells.

Bi X, Jones T, Abbasi F, Lee H, Stultz B, Hursh DA, Mortin MA

Mortin MA, NCI, Biochem Lab, NIH, Bethesda, MD 20892 USA NCI, Biochem Lab, NIH, Bethesda, MD 20892 USA NICHD, Mol Genet Lab, NIH, Bethesda, MD 20892 USA US FDA, Ctr Biol Evaluat & Res, Div Cellular & Gene Therapies, Bethesda, MD 20892 USA

We previously showed that the Drosophila DNA binding homeodomain of Prospero included a 28 amino-acid sequence (HDA) that functions as a nuclear export signal. We describe here the identification of a protein we named Caliban, which can directly interact with the HDA. Caliban is homologous to human Sdccag1, which has been implicated in colon and lung cancer. Here we show that Caliban and Sdccag1 are mediators of nuclear export in fly and human cells, as interference RNA abrogates export of EYFP-HDA in normal fly and human lung cells. Caliban functions as a bipartite mediator nuclear export as the carboxy terminus binds HDA and the amino terminus itself functions as an NES, which directly binds the NES receptor Exportin. Finally, while non-cancerous lung cells have functional Sdccag1, five human lung carcinoma cell lines do not, even though Exportin still functions in these cells. Expression of fly Caliban in these human lung cancer cells restores EYFP-HDA nuclear export, reduces a cell's ability to form colonies on soft agar and reduces cell invasiveness. We suggest that Sdccag1 inactivation contributes to the transformed state of human lung cancer cells and that Caliban should be considered a candidate for use in lung cancer gene therapy.Oncogene (2005) 24, 8229-8239. doi:10.1038/sj.onc.1208962; published online 15 August 2005. Oncogene (2005) 24, 8229-8239. doi:10.1038/sj.onc.1208962; published online 15 August 2005.