A transactivator of c-myc is coordinately regulated with the proto-oncogene during cellular growth.
A recently cloned nuclear protein, which binds a far upstream element (FUSE) of the human c-myc proto-oncogene, stimulates promoter driven expression in undifferentiated cells. In concert with a loss of c-myc expression, both FUSE binding protein (FBP) mRNA and protein levels disappeared in HL60 cells after PMA-induced differentiation, due to a drop in the rate of transcription that was measured by nuclear runoff. During the differentiation of these cells, the brief half-lives of FBP mRNA (3 h) and protein (1.5 h) did not change, allowing for the rapid down-regulation of nuclear protein levels, as detected by immunohistochemical staining. Like c-myc, FBP is expressed in proliferating cells from a variety of lineages, but not in quiescent cells. When T cells and fibroblasts were stimulated to transit from G0 into the cell cycle, there was a dramatic rise of both FBP mRNA and DNA sequence specific nuclear FBP binding activity, which correlated with the appearance of c-myc mRNA. In contrast to the transient expression of many other immediate early growth response genes, both FBP and c-myc expression were sustained for more than 24 h. In fibroblasts, the coordinate expression of FBP and c-myc throughout all phases of the cell cycle is consistent with FBP's role as a growth-dependent regulator of c-myc expression.
Bazar
L
L
Department of Pathology, Georgetown University School of Medicine, Washington, DC 20007, USA.
Harris
V
V
Sunitha
I
I
Hartmann
D
D
Avigan
M
M
D001483:Base Sequence; D002455:Cell Division / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D016259:Genes, myc; D006801:Humans; D007150:Immunohistochemistry; D008969:Molecular Sequence Data; D009838:Oligodeoxyribonucleotides; D011401:Promoter Regions, Genetic; D000090063:Proto-Oncogene Mas; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D015534:Trans-Activators / Q000235:genetics*; D014407:Tumor Cells, Cultured
D004268:DNA-Binding Proteins; C000715470:MAS1 protein, human; D009838:Oligodeoxyribonucleotides; D000090063:Proto-Oncogene Mas; D012333:RNA, Messenger; D015534:Trans-Activators