Induction of hemoglobin synthesis by downregulation of MYB protein with an antisense oligodeoxynucleotide.
Reduced expression of the proto-oncogene c-myb appears necessary for erythroid differentiation induced by chemical agents and by the natural regulator, erythropoietin (Epo). Treatment of Epo-responsive Rauscher erythroleukemia cells with an anti-sense oligodeoxynucleotide to c-myb in the absence of other inducers downregulated myb protein markedly and caused hemoglobinization of the cells within 48 hours. Epo treatment, which downregulates c-myb in these cells, induced hemoglobinization to the same degree. Epo also induced the appearance of anion transport protein on the plasma membrane, consistent with terminal differentiation. In contrast, antisense c-myb did not induce this erythroid marker. The results are consistent with a role for myb protein in the regulation of hemoglobin synthesis.
Chern
Y J
YJ
Department of Medicine, New England Deaconess Hospital, Harvard Medical School, Boston, MA.
O'Hara
C
C
Sytkowski
A J
AJ
D000818:Animals; D027321:Anion Transport Proteins; D002352:Carrier Proteins / Q000378:metabolism; D002462:Cell Membrane / Q000378:metabolism; D004921:Erythropoietin / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects*; D006454:Hemoglobins / Q000096:biosynthesis*; D006801:Humans; D004915:Leukemia, Erythroblastic, Acute; D051379:Mice; D016376:Oligonucleotides, Antisense / Q000494:pharmacology*; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins / Q000235:genetics* / Q000502:physiology; D020598:Proto-Oncogene Proteins c-myb; D014407:Tumor Cells, Cultured
D027321:Anion Transport Proteins; D002352:Carrier Proteins; D006454:Hemoglobins; C000715470:MAS1 protein, human; D016376:Oligonucleotides, Antisense; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins; D020598:Proto-Oncogene Proteins c-myb; D004921:Erythropoietin