Specific covalent binding of a NF-kappaB decoy hairpin oligonucleotide targeted to the p50 subunit and induction of apoptosis.
The NF-kappaB transcriptional factor regulates various functions such as immune responses, cellular growth and development, and is frequently activated in tumor cells. Thus, inhibition of NF-kappaB could suppress tumor cell growth. Using a decoy synthetic hairpin-shaped oligodeoxyribonucleotide (ODN) containing the kappaB site with an integrated single diphosphoryldisulfide linkage, we demonstrate its covalent binding to the p50 subunit of NF-kappaB. Furthermore, this decoy ODN induces apoptosis in a lymphoblastoma cell line. Thus, such chemically modified decoys could be valuable tools for blocking nuclear factors and tumor cell growth.
Lesage
Denis
D
ATHSCO EA3406 Université Paris XIII, Service de Biochimie APHP Hôpital Avicenne, 125 route de Stalingrad, 93009 Cedex, Bobigny, France.
Metelev
Valeri
V
Borisova
Oksana
O
Dolinnaya
Nina
N
Oretskaya
Tatiana
T
Baran-Marszak
Fanny
F
Taillandier
Eliane
E
Raphael
Martine
M
Fagard
Remi
R
D017209:Apoptosis / Q000502:physiology*; D001483:Base Sequence; D001665:Binding Sites; D002455:Cell Division / Q000502:physiology; D002467:Cell Nucleus / Q000378:metabolism; D006801:Humans; D009838:Oligodeoxyribonucleotides / Q000737:chemistry / Q000378:metabolism*; D010455:Peptides / Q000737:chemistry / Q000378:metabolism*; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma; D021122:Protein Subunits / Q000737:chemistry / Q000378:metabolism; D014162:Transfection; D014407:Tumor Cells, Cultured
D009838:Oligodeoxyribonucleotides; D010455:Peptides; D021122:Protein Subunits; C118258:SN50 peptide