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.
Lee
R
R
Huntsman Cancer Institute and Section of Oncology, Department of Medicine, University of Utah, Salt Lake City, UT 84112, USA. ray.lee@hci.utah.edu
Chen
J
J
Matthews
C P
CP
McDougall
J K
JK
Neiman
P E
PE
D000595:Amino Acid Sequence; D030161:Avian Proteins; D016923:Cell Death / Q000235:genetics*; D002460:Cell Line; D002874:Chromosome Mapping; D005260:Female; D049452:Green Fluorescent Proteins; D006801:Humans; D007150:Immunohistochemistry; D007668:Kidney / Q000378:metabolism; D008099:Liver / Q000378:metabolism; D008164:Luminescent Proteins / Q000737:chemistry; D008969:Molecular Sequence Data; D009369:Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D010053:Ovary / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000032:analysis / Q000737:chemistry / Q000235:genetics*; D016415:Sequence Alignment; D014162:Transfection
D030161:Avian Proteins; C117144:BCL2-like 10 protein; D008164:Luminescent Proteins; C118281:Nr13 protein, chicken; D019253:Proto-Oncogene Proteins c-bcl-2; D049452:Green Fluorescent Proteins