Truncated forms of BNIP3 act as dominant negatives inhibiting hypoxia-induced cell death.

BNIP3 (Bcl-2/adenovirus E1B Nineteen Kilodalton Interacting Protein) is a pro-cell death member of the Bcl-2 family of proteins. Its expression is induced by the transcription factor Hypoxia Inducible Factor-1 (HIF-1) under conditions of low oxygen (hypoxia) and is found over expressed in hypoxic regions of many tumors. When over expressed, BNIP3 induces cell death through induction of mitochondrial dysfunction that is dependent on the presence of BNIP3's TM domain.

Anti-tumor chemotherapy utilizing peptide-based approaches--apoptotic pathways, kinases, and proteasome as targets.

The pharmacological sciences are taking advantage of recent discoveries that have defined the molecular pathways governing apoptosis. These signaling cascades are frequently inactivated or distorted by mutations in cancer cells. Peptides derived from critical interaction, phosphorylation, or cleavage sites are the preferred leads (starting points) for the development of new drugs.

Increased expression of Mcl-1 is responsible for the blockage of TRAIL-induced apoptosis mediated by EGF/ErbB1 signaling pathway.

Epidermal growth factor (EGF) protects against death receptor induced apoptosis in epithelial cells. Herein, we demonstrate that EGF protection against tumor necrosis factor related apoptosis-inducing ligand (TRAIL) induced apoptosis is mediated by increased expression of the Bcl-2 family member myeloid cell leukemia 1 (Mcl-1). EGF increased the mRNA and protein levels of Mcl-1.