S-Space College of Medicine/School of Medicine (의과대학/대학원) Program in Cancer Biology (협동과정-종양생물학전공) Journal Papers (저널논문_협동과정-종양생물학전공)
The tail-anchoring domain of Bfl1 and HCCS1 targets mitochondrial membrane permeability to induce apoptosis
- Ko, Jae-Kyun; Choi, Kyoung-Han; Pan, Zui; Lin, Peihui; Weisleder, Noah; Kim, Chul-Woo; Ma, Jianjie
- Issue Date
- Company of Biologists
- J Cell Sci. 2007 Aug 15;120(Pt 16):2912-23. Epub 2007 Jul 31.
- Amino Acid Sequence; *Apoptosis; Base Sequence; Cell Line, Tumor; Conserved Sequence; Humans; Lipid Bilayers/metabolism; Membrane Potential, Mitochondrial; Mitochondrial Membranes/*metabolism; Molecular Sequence Data; Peptides/chemistry; Permeability; Protein Sorting Signals; Protein Structure, Tertiary; Protein Transport; Proto-Oncogene Proteins c-bcl-2/*chemistry/genetics/*metabolism; Structure-Activity Relationship; Tumor Suppressor Proteins/*chemistry/genetics/*metabolism; bcl-2 Homologous Antagonist-Killer Protein/metabolism; bcl-2-Associated X Protein/metabolism
- Many Bcl2 family proteins target intracellular membranes by their C-terminal tail-anchor domain. Bfl1 is a bi-functional Bcl2 family protein with both anti- and pro-apoptotic activities and contains an amphipathic tail-anchoring peptide (ATAP; residues 147-175) with unique properties. Here we show that ATAP targets specifically to mitochondria, and induces caspase-dependent apoptosis that does not require Bax or Bak. Mutagenesis studies revealed that lysine residues flanking the ATAP sequence are involved in targeting of the peptide to the mitochondrial membrane, and charged residues that contribute to the amphipathic nature of ATAP are critical for its pro-apoptotic function. The ATAP sequence is present in another tumor suppressor gene, HCCS1, which contains an additional mitochondria-targeting signal (MTS) close to the ATAP. We propose that both ATAP and MTS could be used as therapeutic peptides to induce cell death in the treatment of cancer cells.
- 0021-9533 (Print)
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