Myb and Ets transcription factors cooperate at the myb-inducible promoter of the tom-1 gene.
Transformation of myeloid cells by the retroviral oncogene v-myb is thought to be caused by deregulated expression of specific cellular genes that act as targets of v-Myb in myeloid cells. Recently, we have identified the chicken tom-1 gene as a direct target for v-Myb. tom-1 has two promoters, only one of which (the tom-1A promoter) is activated by v-Myb. Here, we show that v-Myb activates the tom-1A promoter by cooperating with Ets-2, a member of the Ets transcription factor family. Interestingly, we find that the ability of v-Myb to cooperate with Ets proteins differs from that of its non-oncogenic cellular counterpart c-Myb. c-Myb cooperates with Ets-1 and Ets-2, whereas v-Myb only cooperates with Ets-2. Truncation of the N-terminus of c-Myb, which is known to activate the oncogenic potential of c-Myb, specifically abrogates the ability of the protein to cooperate with Ets-1. Our findings, therefore, reveal a novel function for the N-terminus of c-Myb and raise the possibility that oncogenic activation of c-Myb is linked to the loss of cooperation between Myb and c-Ets-1.
Burk
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Institut für Biochemie, Westfälische-Wilhelms-Universität Münster, Germany.
Klempnauer
K H
KH
D000818:Animals; D001483:Base Sequence; D001665:Binding Sites; D002460:Cell Line; D002472:Cell Transformation, Viral; D002645:Chickens; D004268:DNA-Binding Proteins; D005786:Gene Expression Regulation; D017930:Genes, Reporter; D020570:Genes, myb / Q000235:genetics*; D008969:Molecular Sequence Data; D010957:Plasmids; D017354:Point Mutation; D011401:Promoter Regions, Genetic; D050784:Proto-Oncogene Protein c-ets-1; D050787:Proto-Oncogene Protein c-ets-2; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D050783:Proto-Oncogene Proteins c-ets; D012097:Repressor Proteins; D015682:Retroviridae Proteins, Oncogenic / Q000235:genetics; D015534:Trans-Activators / Q000235:genetics; D014157:Transcription Factors / Q000235:genetics*; D014162:Transfection
D004268:DNA-Binding Proteins; C107465:ERF protein, human; C494041:ETS1 protein, human; D050784:Proto-Oncogene Protein c-ets-1; D050787:Proto-Oncogene Protein c-ets-2; D011518:Proto-Oncogene Proteins; D050783:Proto-Oncogene Proteins c-ets; D012097:Repressor Proteins; D015682:Retroviridae Proteins, Oncogenic; D015534:Trans-Activators; D014157:Transcription Factors; C050379:oncogene proteins v-ets