Characterization of NR13-related human cell death regulator, Boo/Diva, in normal and cancer tissues.

Mouse Boo/Diva is an ovary-specific member of the Bcl-2 family identified through homology with the avian cell death antagonist NR13. We identified a human orthologue of Boo/Diva, which is highly conserved between mouse and human and related to avian NR13. Human Boo/Diva is also expressed in human liver and kidney in addition to the ovary. We found that green fluorescence protein (EGFP)-tagged Boo/Diva was not exclusively localized to mitochondria before the induction of apoptosis. However, EGFP-Boo/Diva translocated to mitochondria in the process of apoptosis induced by vincristine, a microtubule-interfering agent. Overexpression of human Boo/Diva promoted cell death in HeLa and 293 cells. The cell death antagonist Bcl-XL interacts with Boo, but is unable to protect 293 cells from Boo/Diva-induced cell death. Finally, we mapped human Boo/Diva to chromosome 15q21, a locus known to be related to human cervical cancer. Moreover, we found that genomic DNAs of three of 24 human cervical cancer samples display deletions within their Boo/Diva genes. This result suggests a role for human Boo/Diva in the pathogenesis of cervical cancer.