Tumorigenic N-terminal deletions of c-Myb modulate DNA binding, transactivation, and cooperativity with C/EBP.
Oncogenic activation of c-myb by retroviral insertion has been implicated in tumor formation in chicken and mice. These genetic alterations result in deregulated expression of the c-myb gene and frequently in N-terminal truncation of the c-Myb protein. We demonstrate that truncation of the c-Myb N-terminus affects DNA binding and reporter activation. However, all three mutants, Myb Delta N20, Myb Delta N47 and Myb Delta N71 cooperated with C/EBP beta in reporter assays. In contrast to Myb Delta N20 and Myb Delta N47, however, the Myb Delta N71 mutant failed to activate the chromatin embedded endogenous mim-1 gene together with C/EBP beta. This suggests that an N-terminal region (amino acids 47-71) within repeat 1 (R1) of the murine c-Myb DNA binding domain affects activation of chromosomal target genes in collaboration with C/EBP beta.
Oelgeschläger
M
M
Institut für Molekularbiologie, Medizinische Hochschule Hannover, 30623 Hannover, Germany.
Kowenz-Leutz
E
E
Schreek
S
S
Leutz
A
A
Lüscher
B
B
D000123:Acetyltransferases; D000818:Animals; D022782:CCAAT-Enhancer-Binding Protein-beta / Q000378:metabolism*; D019556:COS Cells; D002645:Chickens; D002522:Chlorocebus aethiops; D004247:DNA / Q000378:metabolism*; D004273:DNA, Neoplasm / Q000235:genetics / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D017930:Genes, Reporter; D020570:Genes, myb; D006801:Humans; D008156:Luciferases / Q000096:biosynthesis / Q000235:genetics; D046911:Macromolecular Substances; D051379:Mice; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D011506:Proteins / Q000235:genetics; D020598:Proto-Oncogene Proteins c-myb / Q000737:chemistry / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis; D017384:Sequence Deletion; D014157:Transcription Factors / Q000378:metabolism; D015533:Transcriptional Activation
D022782:CCAAT-Enhancer-Binding Protein-beta; D004273:DNA, Neoplasm; D046911:Macromolecular Substances; D011506:Proteins; D020598:Proto-Oncogene Proteins c-myb; D011993:Recombinant Fusion Proteins; D014157:Transcription Factors; C099810:transcription factor NF-M; D004247:DNA; D008156:Luciferases; D000123:Acetyltransferases; C077509:mim-1 protein, Gallus gallus