Adenovirus E1B-19K/BCL-2 interacting protein BNIP3 contains a BH3 domain and a mitochondrial targeting sequence

J Biol Chem. 1998 May 15;273(20):12415-21. doi: 10.1074/jbc.273.20.12415.


Adenovirus E1B-19K and BCL-2 anti-apoptosis proteins interact with certain BCL-2 family pro-apoptotic proteins. A conserved domain, BH3, present in these proteins is essential for their pro-apoptotic activity and for heterodimerization with anti-apoptosis proteins. Cellular protein BNIP3 (previously NIP3) interacts with E1B-19K, BCL-2, BCL-xL, and EBV-BHRF1. BNIP3 contains a motif similar to the BH3 domain. Deletion of the BH3-like motif in BNIP3 abrogates its ability to heterodimerize with E1B-19K and BCL-xL. Substitution of the BH3 domain of BNIP3 for the corresponding sequences of BAX functionally restores the pro-apoptotic and protein heterodimerization activities of BAX. BNIP3 exhibits a delayed cell death activity that is partially relieved by deletion of the BH3 domain. BNIP3 suppresses the anti-apoptosis activity of BCL-xL in a BH3-dependent manner. BNIP3 contains a C-terminal trans-membrane (TM) domain similar to other BCL-2 family proteins and BNIP1 (previously NIP1). The TM domains of BNIP3 and BNIP1 can functionally substitute for the TM domain of a BCL-2 family member EBV-BHRF1. The BNIP3 TM domain exclusively targets the heterologous green fluorescent protein (GFP) to mitochondria. These results suggest that BNIP3 is a member of the BH3-contaning BCL-2 family of pro-apoptotic proteins and functions in mitochondria.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adenovirus E1B Proteins / metabolism*
  • Amino Acid Sequence
  • Animals
  • Apoptosis
  • COS Cells
  • Membrane Proteins / chemistry*
  • Membrane Proteins / metabolism
  • Mitochondria / metabolism*
  • Molecular Sequence Data
  • Proto-Oncogene Proteins / chemistry*
  • Proto-Oncogene Proteins / metabolism
  • Proto-Oncogene Proteins c-bcl-2 / metabolism*
  • Sequence Deletion
  • Subcellular Fractions / metabolism
  • Tumor Suppressor Proteins*
  • bcl-2-Associated X Protein


  • Adenovirus E1B Proteins
  • BNIP3 protein, human
  • BNIP3L protein, human
  • Membrane Proteins
  • Proto-Oncogene Proteins
  • Proto-Oncogene Proteins c-bcl-2
  • Tumor Suppressor Proteins
  • bcl-2-Associated X Protein