v-Myb represses the transcription of Ets-2.
The v-Myb oncogene causes monoblastic leukemia and transforms only myelomonocytic cells in culture. The v-Myb protein is nuclear and binds to specific DNA sequences. To identify genes regulated by v-Myb, we utilized primary cells transformed by a retrovirus encoding a v-Myb-estrogen receptor (ER) fusion protein. The Ets-2 gene was not expressed in v-Myb-ER transformed cells in the presence of estradiol, but was expressed within 4 h after estradiol withdrawal. The expression of Ets-2 also increased dramatically following phorbol ester-induced differentiation of the v-Myb-transformed BM2 cell line. Conversely, CRYP-alpha, encoding a transmembrane tyrosine phosphatase, was expressed in the presence but not the absence of estradiol in v-Myb-ER transformed cells. CRYP-alpha was downregulated during the phorbol ester-induced differentiation of BM2 cells. Although LIM-3 expression was estradiol-inducible in v-Myb-ER transformed monoblasts, LIM-3 was expressed neither in primary yolk sac cells transformed by unfused v-Myb nor in BM2 cells. We conclude that although v-Myb has been intensively studied as a transcriptional activator, v-Myb can repress biologically relevant genes such as Ets-2, which promotes macrophage differentiation. In addition, we have shown that some genes that are regulated by a v-Myb-ER fusion protein may not be relevant to the biological function of the unfused v-Myb protein.
Wang
D-M
DM
Department of Pathology, Stanford University School of Medicine, Stanford, CA 94305-5324, USA.
Sevcikova
S
S
Wen
H
H
Roberts
S
S
Lipsick
J S
JS
D000818:Animals; D030161:Avian Proteins / Q000235:genetics; D002352:Carrier Proteins / Q000235:genetics; D002454:Cell Differentiation; D002642:Chick Embryo; D015536:Down-Regulation; D004958:Estradiol / Q000494:pharmacology; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D006801:Humans; D020626:Oncogene Proteins v-myb / Q000235:genetics / Q000378:metabolism*; D017027:Protein Tyrosine Phosphatases / Q000235:genetics; D050787:Proto-Oncogene Protein c-ets-2 / Q000235:genetics*; D012333:RNA, Messenger / Q000032:analysis / Q000378:metabolism; D054557:Receptor-Like Protein Tyrosine Phosphatases; D011960:Receptors, Estrogen / Q000235:genetics / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic; D015017:Yolk Sac / Q000166:cytology / Q000187:drug effects / Q000378:metabolism
D030161:Avian Proteins; D002352:Carrier Proteins; D020626:Oncogene Proteins v-myb; D050787:Proto-Oncogene Protein c-ets-2; D012333:RNA, Messenger; D011960:Receptors, Estrogen; D011993:Recombinant Fusion Proteins; D012097:Repressor Proteins; D004958:Estradiol; C490606:CRYPalpha protein, Gallus gallus; D017027:Protein Tyrosine Phosphatases; D054557:Receptor-Like Protein Tyrosine Phosphatases