The adenovirus E1B protein is a viral homolog of the Bcl-2 family of proteins that are involved in regulating cell death. A family of interacting proteins, which are designated Nip or Bnip and include BNIP-1, BNIP-2, BNIP-3 and Nix, associate with both the E1B protein and Bcl-2 proteins to mediate apoptotic signaling. BNIP-1 contains a hydrophobic transmembrane domain, which enables its localization to the nuclear envelope, endoplasmic recticulum and mitochondria. BNIP-2, (previously designated Nip2 and Nip21 in human and mouse respectively), shares homology with the non-catalytic domain of Cdc42 GTPase-activating protein (Cdc42GAP). Through binding to Cdc42GAP, BNIP-2 enhances the GTPase activity of Cdc42GAP, facilitating the hydrolysis of GTP bound to Cdc42 and thereby, mediating the signaling pathways involving receptor kinases, small GTPases and apoptotic proteins. Nix, which is also designated Nip3L or Bnip3L, is highly related to BNIP-3, and both proteins localize to the mitochondria where they associate with Bcl-2 proteins. BNIP-3 preferentially binds to Bcl-xL and induces apoptosis by suppressing the anti-apoptosis activity of Bcl-xL.