Inhibition of protein-tyrosine kinase activity in intact cells by the aptameric action of oligodeoxynucleotides.
Direct interaction of oligodeoxynucleotides (ODNs) with proteins represents one of the nonantisense-mediated effects of ODNs. Phosphorothioate-capped ODNs have been shown to inhibit directly the in vitro kinase activity of the chronic myelogenous leukemia-associated protein-tyrosine kinase p210bcr-abl. In this study we have determined the efficacy of this aptameric ODN in a cellular system using the K562 chronic myelogenous leukemia-derived cell line. Significant effects upon cellular phosphotyrosine content, as well as cellular growth in soft agar, are observed. These effects are sequence specific and are not mediated through changes in p210bcr-abl protein levels. Additional ODNs are described that also reduce cellular phosphotyrosine levels and inhibit growth in soft agar but do not inhibit p210bcr-abl kinase activity in vitro.
Bergan
R C
RC
Medical Oncology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
Kyle
E
E
Connell
Y
Y
Neckers
L
L
D001483:Base Sequence; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D016044:Fusion Proteins, bcr-abl / Q000378:metabolism*; D006801:Humans; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive; D008969:Molecular Sequence Data; D016376:Oligonucleotides, Antisense / Q000138:chemical synthesis / Q000494:pharmacology*; D019000:Phosphotyrosine; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D013329:Structure-Activity Relationship; D014407:Tumor Cells, Cultured; D014443:Tyrosine / Q000031:analogs & derivatives / Q000032:analysis
D016376:Oligonucleotides, Antisense; D019000:Phosphotyrosine; D014443:Tyrosine; D011505:Protein-Tyrosine Kinases; D016044:Fusion Proteins, bcr-abl