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 t hrough homology with the avian cell death antagonist NR13, We identified a human orthologue of Boo/Diva, which is highly conserved between mouse and h uman and related to avian NR13. Human Boo/Diva is also expressed in human l iver and kidney in addition to the ovary. We found that green fluorescence protein (EGFP)-tagged Boo/Diva was not exclusively localized to mitochondri a before the induction of apoptosis. However, EGFP-Boo/Diva translocated to mitochondria in the process of apoptosis induced by vincristine. a microtu bule-interfering agent. Overexpression of human Boo/Diva promoted cell deat h in HeLa and 293 cells. The cell death antagonist Bcl-XL interacts with Bo o. but is unable to protect 293 cells from Boo/ Diva-induced cell death. Fi nally, we mapped human Boo/Diva to chromosome 15q21, a locus known to be re lated to human cervical cancer. Moreover. we found that genomic DNAs of thr ee of 24 human cervical cancer samples display deletions Nk within their Bo o/Diva genes. This result suggests a role for human Boo/Diva in the pathoge nesis of cervical cancer. (C) 2001 Elsevier Science B.V. All rights reserve d.