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Interaction of G‐rich GT oligonucleotides with nuclear‐associated eEF1A is correlated with their antiproliferative effect in haematopoietic human cancer cell lines
Author(s) -
Scaggiante Bruna,
Dapas Barbara,
Grassi Gabriele,
Manzini Giorgio
Publication year - 2006
Publication title -
the febs journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 204
eISSN - 1742-4658
pISSN - 1742-464X
DOI - 10.1111/j.1742-4658.2006.05143.x
Subject(s) - cytotoxicity , nucleolin , oligonucleotide , lymphoblast , haematopoiesis , biology , nuclear protein , cell culture , cancer cell , biochemistry , in vitro , microbiology and biotechnology , chemistry , dna , cancer , cytoplasm , stem cell , transcription factor , genetics , gene , nucleolus
G‐rich GT oligonucleotides with a different content of G clusters have been evaluated for their ability to exert cytotoxicity and to bind to nuclear‐associated proteins in T‐lymphoblast CCRF‐CEM cells. Only the oligomers that did not form G‐based structures or had a poor structure, under physiological conditions, were able to exert significant cellular growth inhibition effect. The cytotoxicity of these oligomers was related to their binding to the nuclear‐associated eEF1A protein, but not to the recognition of nucleolin or other proteins. In particular, GT oligomers adopting a conformation compatible with G‐quadruplex, did not exert cytotoxicity and did not bind to eEF1A. The overall results suggest that the ability of oligomers to adopt a G‐quadruplex‐type secondary structure in a physiological buffer containing 150 m m NaCl is not a prerequisite for antiproliferative effect in haematopoietic cancer cells. The cytotoxicity of G‐rich GT oligomers was shown to be tightly related to their binding affinity for eEF1A protein.