The BH3 alpha-helical mimic BH3-M6 disrupts Bcl-X(L), Bcl-2, and MCL-1 protein-protein interactions with Bax, Bak, Bad, or Bim and induces apoptosis in a Bax- and Bim-dependent manner.

Journal article

A critical hallmark of cancer cell survival is evasion of apoptosis. This is commonly due to overexpression of anti-apoptotic proteins such as Bcl-2, Bcl-X(L), and Mcl-1, which bind to the BH3 α-helical domain of pro-apoptotic proteins such as Bax, Bak, Bad, and Bim, and inhibit their function. We designed a BH3 α-helical mimetic BH3-M6 that binds to Bcl-X(L) and Mcl-1 and prevents their binding to fluorescently labeled Bak- or Bim-BH3 peptides in vitro. Using several approaches, we demonstra...

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Authors: Kazi, A; Sun, J; Doi, K; Sung, S; Takahashi, Y

• Publication status: Published
• Journal: Journal of biological chemistry
• Volume: 286
• Issue: 11
• Pages: 9382-9392
• Publication date: 2011-03-01
• DOI: 10.1074/jbc.m110.203638
• EISSN: 1083-351X
• ISSN: 0021-9258
• Language: English
• Keywords: Animals; bcl-Associated Death Protein; bcl-2 Homologous Antagonist-Killer Protein; Proteasome Endopeptidase Complex; Membrane Proteins; BH3 Interacting Domain Death Agonist Protein; Dipeptides; HEK293 Cells; Humans; Cell Line, Tumor; bcl-X Protein; Protease Inhibitors; Protein Structure, Tertiary; Apoptosis Regulatory Proteins; Cytochromes c; Apoptosis; Proteasome Inhibitors; Proto-Oncogene Proteins; Mitochondria; Phthalimides; bcl-2-Associated X Protein; Peptide Fragments; Proto-Oncogene Proteins c-bcl-2; Caspase 3