Functional Dissection of BH3 Only Protein BNIP3

概要

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BNIP3 is a pro-apoptotic protein, which contains BH3 and trans-membrane domains. Previous studies demonstrated an association between ceBNIP3, C. elegans homologue of BNIP3, and ced-3. It seemed likely that the interaction between ceBNIP3 and ced-3 was an alternative cascade of caspase activation in C. elegans, however the detailed mechanism of this interaction is yet to be elucidated. We constructed several deletion mutants of BNIP3 and investigated their biological functions. As we expected, the trans-membrane domain of BNIP3 was not required for the association between BNIP3 and ced-3, however trans-membrane deletion mutant could not initiate the apoptotic cascade. Immunofluorescence study demonstrated that wild type BNIP3 and ced-3 co-localized on mitochondria, but trans-membrane deletion mutant did not. These results suggest that the recruitment of ced-3/caspase onto the mitochondrial membrane is essential for BNIP3 initiated apoptosis.
札幌医科大学の論文