Autocrine growth induced by kinase type oncogenes in myeloid cells requires AP-1 and NF-M, a myeloid specific, C/EBP-like factor.
The nuclear oncogenes v-myc or v-myb specifically transform avian myeloid cells. In both cases, the transformed cells remain dependent on chicken myelomonocytic growth factor (cMGF). This factor dependence can be relieved by expression of kinase-type oncogenes such as v-mil or v-erbB, leading to expression of cMGF and autocrine growth stimulation. In erythroid cells the same kinase-type oncogenes cause transformation but do not induce cMGF expression. Here we investigated the molecular mechanisms of the observed lineage specific oncogene collaboration. We found that kinase-type oncogenes and TPA activate the cMGF promoter via AP-1 like transcription factors. The activation of the cMGF promoter is, however, strictly dependent on the binding of nuclear proteins to both halves of an inverted repeat adjacent to the AP-1 binding site. These proteins are related to C/EBP. They are expressed exclusively in myeloid cells and were therefore termed NF-M. Our results indicate that the lineage specific cooperation of kinase type oncogenes with v-myb or v-myc in leukemia formation is based on the concerted action of AP-1 and NF-M on the cMGF promoter.
Sterneck
E
E
Zentrum für Molekulare Biologie Heidelberg, University of Heidelberg, FRG.
Müller
C
C
Katz
S
S
Leutz
A
A
D000818:Animals; D030161:Avian Proteins; D001483:Base Sequence; D002454:Cell Differentiation; D002478:Cells, Cultured; D002645:Chickens; D016207:Cytokines; D004252:DNA Mutational Analysis; D005786:Gene Expression Regulation; D006133:Growth Substances / Q000235:genetics*; D036341:Intercellular Signaling Peptides and Proteins; D008957:Models, Genetic; D008969:Molecular Sequence Data; D005810:Multigene Family; D009841:Oligonucleotides / Q000138:chemical synthesis / Q000378:metabolism; D018739:Oncogene Proteins v-erbB; D027384:Oncogene Proteins v-raf; D009857:Oncogenes / Q000235:genetics*; D011401:Promoter Regions, Genetic / Q000235:genetics; D011494:Protein Kinases / Q000378:metabolism; D016755:Proto-Oncogene Proteins c-jun / Q000494:pharmacology; D012045:Regulatory Sequences, Nucleic Acid / Q000235:genetics*; D015682:Retroviridae Proteins, Oncogenic / Q000235:genetics; D014157:Transcription Factors / Q000235:genetics*
D030161:Avian Proteins; D016207:Cytokines; D006133:Growth Substances; D036341:Intercellular Signaling Peptides and Proteins; C059626:MGF protein, chicken; D009841:Oligonucleotides; D018739:Oncogene Proteins v-erbB; D016755:Proto-Oncogene Proteins c-jun; D015682:Retroviridae Proteins, Oncogenic; D014157:Transcription Factors; D011494:Protein Kinases; D027384:Oncogene Proteins v-raf