Differential binding of nuclear c-ets-1 protein to an intron I fragment of the c-myb gene in growth versus differentiation.
For growth, ML-1 human myeloblastic leukemia cells require insulin-like growth factor 1 together with transferrin, whereas for differentiation they depend upon transforming growth factor beta in combination with transferrin. As shown in this study, growth stimulation is accompanied by c-myb expression, whereas initiation of differentiation results in the cessation of c-myb expression through premature termination of transcription in the first intron of the myb gene. Growth factor-stimulated c-myb elongation was found to correlate with an elevated level of nuclear c-ets-1 protein and with increased binding of this protein to an 18-base pair sequence in intron 1 of the c-myb gene containing the putative regulatory element PEA 3. In contrast, differentiation factor-initiated ML-1 cell maturation was accompanied by a very low level of nuclear c-ets-1 protein, by the inability to detect binding of the protein to the 18-base pair sequence, and by the cessation of c-myb expression. These results show a correlation to exist between c-ets-1 binding to intron 1 of the c-myb gene and c-myb expression. The mechanism underlying this correlation is under further study.
Roswell Park Cancer Institute, Grace Cancer Drug Center, Buffalo, New York 14263.
L G
LG
Wang
X M
XM
Liu
Z R
ZR
Li
S
S
Denstman
A
A
Bloch
D001483:Base Sequence; D002454:Cell Differentiation / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D004247:DNA / Q000378:metabolism*; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology; D007438:Introns / Q000235:genetics*; D007951:Leukemia, Myeloid / Q000473:pathology; D008969:Molecular Sequence Data; D009687:Nuclear Proteins / Q000378:metabolism; D009857:Oncogenes / Q000235:genetics*; D011518:Proto-Oncogene Proteins / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D050783:Proto-Oncogene Proteins c-ets; D020598:Proto-Oncogene Proteins c-myb; D012333:RNA, Messenger / Q000096:biosynthesis; D014157:Transcription Factors / Q000378:metabolism*; D015533:Transcriptional Activation / Q000187:drug effects; D014168:Transferrin / Q000494:pharmacology; D016212:Transforming Growth Factor beta / Q000494:pharmacology; D014407:Tumor Cells, Cultured
D009687:Nuclear Proteins; D011518:Proto-Oncogene Proteins; D050783:Proto-Oncogene Proteins c-ets; D020598:Proto-Oncogene Proteins c-myb; D012333:RNA, Messenger; D014157:Transcription Factors; D014168:Transferrin; D016212:Transforming Growth Factor beta; D007334:Insulin-Like Growth Factor I; D004247:DNA