Cleavage of BNIP-2 and BNIP-XL by caspases

• Published in: Biochemical and biophysical research communications 2007-12, Vol.364 (3), p.495-501
• Main Authors: Valencia, C. Alexander, Cotten, Steven W., Liu, Rihe
• Format: Article
• Language: English
• Subjects: Adaptor Proteins, Signal Transducing - metabolism; Apoptosis; Apoptosis Regulatory Proteins - metabolism; BCH domain; BNIP-2; BNIP-XL; Breast Neoplasms - metabolism; Breast Neoplasms - pathology; Caspase substrates; Caspases - chemistry; Caspases - metabolism; Cell Line; Cleavage of functional domains; EF-hand motif; Humans; Neoplasm Proteins - metabolism; Proapoptotic protein; Substrate Specificity
• ISSN: 0006-291X; 1090-2104
• DOI: 10.1016/j.bbrc.2007.10.018

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.