Suppression of receptor-mediated apoptosis by death effecter domain recruiting domain binding peptide aptamer.

FLASH protein is a component of death-inducing signaling complex and might be involved in death receptor-mediated extrinsic apoptosis. Here we developed the peptide aptamer against death effecter domain recruiting domain (DRD) of FLASH protein and showed that the peptide bound to FLASH protein in vitro. Intracellular expression of the DRD-binding peptide aptamer specifically suppressed receptor-mediated extrinsic apoptosis but not intrinsic pathway, which was recapitulated by the antisense oligonucleotides for FLASH. These data suggest that DRD-binding peptide is not only a novel inhibitor modulating receptor-mediated apoptosis but also a tool for elucidating the roles of FLASH in apoptosis.

[1]  F. Hoppe-Seyler,et al.  Peptide aptamers: specific inhibitors of protein function. , 2004, Current molecular medicine.

[2]  Jaehoon Yu,et al.  Mimicry of tandem repeat peptides against cell surface carbohydrates. , 2002, Journal of the American Chemical Society.

[3]  J. Medema.  Apoptosis: Life and death in a FLASH , 1999, Nature.

[4]  G. P. Smith,et al.  Libraries of peptides and proteins displayed on filamentous phage. , 1993, Methods in enzymology.

[5]  J. Marín-García,et al.  Mitochondrial signaling pathways: A receiver/integrator organelle , 2004, Molecular and Cellular Biochemistry.

[6]  R. Hoess,et al.  Protein design and phage display. , 2001, Chemical reviews.

[7]  Roger Y. Tsien,et al.  Crystal Structure of the Aequorea victoria Green Fluorescent Protein , 1996, Science.

[8]  Sunjoo Jeong,et al.  Inhibition of the angiogenesis by the MCP‐1 (monocyte chemoattractant protein‐1) binding peptide , 2005, FEBS letters.

[9]  B. Kay,et al.  Screening phage-displayed combinatorial peptide libraries. , 2001, Methods.

[10]  C. Chung,et al.  Atypical role of proximal caspase-8 in truncated Tau-induced neurite regression and neuronal cell death , 2003, Neurobiology of Disease.

[11]  T R Hughes,et al.  Genetic selection of peptide inhibitors of biological pathways. , 1999, Science.

[12]  Matthias Mann,et al.  FLICE, A Novel FADD-Homologous ICE/CED-3–like Protease, Is Recruited to the CD95 (Fas/APO-1) Death-Inducing Signaling Complex , 1996, Cell.

[13]  M. Peter,et al.  The CD95(APO-1/Fas) DISC and beyond , 2003, Cell Death and Differentiation.

[14]  B. Kay,et al.  Convergent evolution with combinatorial peptides , 2000, FEBS letters.

[15]  R. W. Janes,et al.  Screening of a library of phage-displayed peptides identifies human bcl-2 as a taxol-binding protein. , 1999, Journal of molecular biology.

[16]  K. Sakamaki,et al.  The CED-4-homologous protein FLASH is involved in Fas-mediated activation of caspase-8 during apoptosis , 1999, Nature.

[17]  D. Fowlkes,et al.  Peptide antagonists of the human estrogen receptor. , 1999, Science.

[18]  G. Nolan,et al.  Dominant effector genetics in mammalian cells , 2001, Nature Genetics.

[19]  M. Peter,et al.  Cytotoxicity‐dependent APO‐1 (Fas/CD95)‐associated proteins form a death‐inducing signaling complex (DISC) with the receptor. , 1995, The EMBO journal.