The deazaguanine-derivative, queuine, affects cell proliferation, protein phosphorylation and the expression of the proto oncogenes c-fos and c-myc in HeLa cells.
In higher eukaryotes the hypermodified guanine analogue, queuine (7-(5-[(1S,4S,5R)-4,5-dihydroxy-2-cyclopentene-1-yl) amino)-methyl)-7-deazaguanine), occurs free or as modified nucleoside (Q) in the anticodon of specific tRNAs. Fast proliferating tissues and tumors contain considerable amounts of free queuine and Q-deficient tRNAs. Here we show that HeLa cells can be grown in the absence or presence of queuine. In response to queuine, and under appropriate conditions, (i) the proliferation of HeLa cells was stimulated, (ii) the steady-state level of c-fos mRNA was reduced, contrary that of c-myc mRNA was elevated, and (iii) in cytosolic extracts protein phosphorylation especially for a 42 kDa protein was significantly increased. The results suggest that queuine substitutes for growth factors in a signal transduction pathway.
Langgut
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W
Institut für Biochemie, Med. Fak., Universität Erlangen-Nürnberg, FRG.
Kersten
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H
D015152:Blotting, Northern; D002455:Cell Division / Q000187:drug effects; D003600:Cytosol / Q000378:metabolism; D015870:Gene Expression / Q000187:drug effects*; D006147:Guanine / Q000031:analogs & derivatives* / Q000494:pharmacology; D006367:HeLa Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D007700:Kinetics; D009363:Neoplasm Proteins / Q000378:metabolism; D010766:Phosphorylation; D011505:Protein-Tyrosine Kinases / Q000235:genetics; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D016760:Proto-Oncogene Proteins c-fos; D016271:Proto-Oncogene Proteins c-myc; D011519:Proto-Oncogenes; D012334:RNA, Neoplasm / Q000235:genetics / Q000302:isolation & purification
D009363:Neoplasm Proteins; D011518:Proto-Oncogene Proteins; D016760:Proto-Oncogene Proteins c-fos; D016271:Proto-Oncogene Proteins c-myc; D012334:RNA, Neoplasm; D006147:Guanine; C019549:queuine; D011505:Protein-Tyrosine Kinases