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PMID:9731710

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Citation

Hsu, SY, Lin, P and Hsueh, AJ (1998) BOD (Bcl-2-related ovarian death gene) is an ovarian BH3 domain-containing proapoptotic Bcl-2 protein capable of dimerization with diverse antiapoptotic Bcl-2 members. Mol. Endocrinol. 12:1432-40

Abstract

Using the yeast two-hybrid protein-protein interaction system to search for genes capable of forming dimers with the antiapoptotic protein Mcl-1, we have isolated BOD (Bcl-2-related ovarian death agonist) from an ovarian fusion cDNA library. The three variants of BOD (long, medium, and short) have an open reading frame of 196, 110, and 93 amino acids, respectively; all of them contain a consensus Bcl-2 homology 3 (BH3) domain but lack other BH domains found in channel-forming Bcl-2 family proteins. In the yeast cell assay, BOD interacts with diverse antiapoptotic Bcl-2 proteins [Mcl-1, Bcl-2, Bcl-xL, Bcl-w, Bfl-1, and Epstein-Barr virus (EBV) BHRF-1] but not with different proapoptotic Bcl-2 proteins (BAD, Bak, Bok, and Bax). After overexpression in mammalian Chinese hamster ovary (CHO) cells, BOD induces apoptosis that can be prevented by the baculoviral caspase inhibitor P35. The cell-killing activity of BOD is also antagonized in cells cotransfected with the antiapoptotic Bcl-w protein, which showed high affinity for BOD in the two-hybrid assay. Furthermore, mutagenesis studies showed that BOD mutants with alterations in the BH3 domain lose cell-killing ability, suggesting that the BH3 domain is important for the mediation of cell killing by BOD. BOD mRNA is ubiquitously expressed in ovary and multiple other tissues. The BOD gene is also conserved in diverse mammalian species. Identification of BOD expands the group of proapoptotic Bcl-2 proteins that only contains the BH3 domain and allows future elucidation of the intracellular mechanism for apoptosis regulation in ovary and other tissues.

Links

PubMed

Keywords

Alternative Splicing; Amino Acid Sequence; Animals; Apoptosis; Apoptosis Regulatory Proteins; CHO Cells; Carrier Proteins/chemistry; Carrier Proteins/genetics; Carrier Proteins/metabolism; Cricetinae; Dimerization; Humans; Membrane Proteins; Molecular Sequence Data; Neoplasm Proteins/metabolism; Proto-Oncogene Proteins; Proto-Oncogene Proteins c-bcl-2/chemistry; Proto-Oncogene Proteins c-bcl-2/genetics; Proto-Oncogene Proteins c-bcl-2/metabolism; RNA, Messenger/metabolism; Rats

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

HUMAN:B2L11

involved_in

GO:0006915: apoptotic process

ECO:0000304: author statement supported by traceable reference used in manual assertion

P

Seeded From UniProt

complete

RAT:B2L11

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

RGD:2200

F

Seeded From UniProt

complete

RAT:B2L11

involved_in

GO:0010942: positive regulation of cell death

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

RAT:B2CL1

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

RGD:628774

F

Seeded From UniProt

complete


See also

References

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