Cleavage of BNIP-2 and BNIP-XL by caspases.
BNIP-2 and BNIP-XL are BCH domain-containing proteins that are implicated in programmed cell death. It has been reported that overexpression of BNIP-2 in neuroblastoma cell lines resulted in massive cell death, whereas BNIP-XL was upregulated during NGF-depletion-induced apoptosis in neuroblastoma and was involved in the regulation of differentiation, survival, and aggressiveness of tumor cells. Despite their importance in apoptosis, our understanding of BNIP-2 containing proteins is limited. In this communication, we demonstrate that both BNIP-2 and BNIP-XL are cleaved by caspases during apoptosis. Significantly, the caspase cleavage sites on BNIP-2 are located on its N-terminal EF-hand motif, while that on BNIP-XL is located upstream of the C-terminal BCH domain. Our results suggest that the caspase-mediated cleavage of BNIP-2 and BNIP-XL could result in the release of the BCH domain or smaller fragments that are crucial for their proapoptotic activities.
Valencia
C Alexander
CA
School of Pharmacy and Carolina Center for Genome Sciences, The University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
Cotten
Steven W
SW
Liu
Rihe
R
D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism*; D017209:Apoptosis; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism*; D001943:Breast Neoplasms / Q000378:metabolism* / Q000473:pathology*; D020169:Caspases / Q000737:chemistry / Q000378:metabolism*; D002460:Cell Line; D006801:Humans; D009363:Neoplasm Proteins / Q000378:metabolism*; D013379:Substrate Specificity
D048868:Adaptor Proteins, Signal Transducing; D051017:Apoptosis Regulatory Proteins; C450834:BNIPL protein, human; D009363:Neoplasm Proteins; C509845:PRUNE2 protein, human; D020169:Caspases