Back-mutation of the V-Ets to the C-Ets carboxy-terminal amino acids in the P135gag-myb-ets results in chicken neuroretina cells transformation and loss of basic fibroblast growth factor responsiveness.
The v-Myb, v-Ets containing E26 retrovirus (called in this work E26ABC) induces the proliferation of chicken neuroretina (CNR) cells in minimal medium, strongly stimulated by basic Fibroblast Growth Factor (bFGF) which confers on them the ability to form colonies in soft agar. V-Ets differs from its cellular counterpart c-Ets-1 by two point mutations and by the replacement of the 13 last C-terminal amino acids by 16 unrelated residues as a consequence of DNA segment inversion in the viral sequence. It has been documented that this different C-terminal sequence influences DNA binding activity and specificity. Replacement in E26ABC virus of the sequence encoding the 16 v-Ets last C-terminal amino acids by the sequence encoding the 13 c-Ets-1 derived C-terminus (virus E26ABO), results in the production of a P135gag-myb-ets with modified biological properties on CNR cells. E26ABO infected CNR cells proliferate in minimal medium more efficiently than E26ABC, are unresponsive to bFGF and able to grow in soft agar. In contrast, CNR cells infected by viruses encoding Myb and Ets proteins either in the E26ABO or in the E26ABC configuration are bFGF responsive. Since Myb alone is sufficient to induce bFGF responsiveness on CNR cells, these results suggest that the c-Ets-1 C-terminus interferes with the Myb activity of the E26ABO P135gag-myb-ets protein in CNR cells.
Garrido
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C
CNRS EP56, Institut Pasteur de Lille, France.
Leprince
D
D
Plaza
S
S
Aumercier
M
M
Stéhelin
D
D
Saule
S
S
D000818:Animals; D001483:Base Sequence; D002455:Cell Division / Q000187:drug effects; D002461:Cell Line, Transformed; D002645:Chickens; D015342:DNA Probes; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology*; D015750:Genes, gag; D008969:Molecular Sequence Data; D009154:Mutation; D009857:Oncogenes; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D050783:Proto-Oncogene Proteins c-ets; D012165:Retinal Ganglion Cells / Q000473:pathology*; D015682:Retroviridae Proteins, Oncogenic / Q000235:genetics*; D014157:Transcription Factors / Q000235:genetics*; D014158:Transcription, Genetic
D015342:DNA Probes; D011518:Proto-Oncogene Proteins; D050783:Proto-Oncogene Proteins c-ets; D015682:Retroviridae Proteins, Oncogenic; D014157:Transcription Factors; C050379:oncogene proteins v-ets; D016222:Fibroblast Growth Factor 2