Description
The Bcl-2 nineteen kilodalton interacting protein 3 (BNIP3 or NIP3), is a hypoxia-inducible proapoptotic member of the Bcl-2 family that induces cell death by associating with the mitochondria. BNIP3, expressed in skeletal muscle and in the brain at low levels, is primarily localized to the nucleus of glial cells of the normal human brain, as well as in the malignant glioma cell line U251. BNIP3 expression in the cytoplasm increases and localizes with the mitochondria, contributing to induction of cell death. Cellular protein BNIP3 interacts with E1B-19K, BCL-2, BCL-xL, and EBV-BHRF1. BNIP3 contains Bcl-2 homology 3 (BH3) domain and COOH-terminal transmembrane (TM) domain. The BH3 domain of BNIP3 mediates Bcl-2/Bcl-X(L) heterodimerization and confers pro-apoptotic activity; whereas the TM domain is critical for homodimerization, pro-apoptotic function, and mitochondrial targeting