Modulation of Nr-13 antideath activity by peptide aptamers.
Tumor cells are characterized by deregulated proliferation and resistance to proapoptotic stimuli. The Bcl-2 family of antiapoptotic proteins is overexpressed in a large number of chemoresistant tumors. Downregulation or inhibition of antiapoptotic proteins might result in the sensitization of cancer cells to chemotherapeutic agents. In the present study, we took advantage of the peptide aptamer strategy to target Nr-13, a Bcl-2 antiapoptotic protein involved in neoplastic transformation by the Rous sarcoma virus. We isolated peptide aptamers that behave as Nr-13 regulators, in vitro and in mammalian cells in culture. Some of these aptamers have potential proapoptotic activities. These data suggest that peptide aptamers targeting the Bcl-2 family of apoptosis inhibitors may be useful for the development of anticancer molecules.
Nouvion
A-L
AL
Equipe Apoptose et Oncogenèse, Institut de Biologie et Chimie des Protéines (IBCP UMR 5086 CNRS/Université claude Bernard Lyon 1), IFR128 BioSciences Lyon-Gerland, Lyon, France.
Thibaut
J
J
Lohez
O D
OD
Venet
S
S
Colas
P
P
Gillet
G
G
Lalle
P
P
D000595:Amino Acid Sequence; D000818:Animals; D017209:Apoptosis; D052158:Aptamers, Peptide / Q000494:pharmacology*; D019556:COS Cells / Q000187:drug effects; D053148:Caspase 3 / Q000378:metabolism; D002522:Chlorocebus aethiops; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D008969:Molecular Sequence Data; D009865:Oocytes / Q000378:metabolism; D019151:Peptide Library; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism*; D052736:Rous sarcoma virus / Q000235:genetics; D020798:Two-Hybrid System Techniques; D014982:Xenopus laevis / Q000378:metabolism
D052158:Aptamers, Peptide; D019151:Peptide Library; D019253:Proto-Oncogene Proteins c-bcl-2; D011065:Poly(ADP-ribose) Polymerases; D053148:Caspase 3