c-Myb function in fibroblasts.
The protooncogene c-myb is a nuclear transcription factor that shares significant sequence homology with two other myb family members, A-myb and B-myb. Recent studies have suggested that c-myb is involved in regulation of the cell cycle via control of intracellular calcium [Ca2+]i concentration. Given the limited cell type expression of the c-myb gene, we set out to investigate whether myb-dependent cell cycle regulation occurs in cells not known to express the c-myb protein. NIH 3T3 fibroblasts were stably transfected with an inducible c-myb dominant negative construct composed of a myb DNA binding domain linked to the Drosophila engrailed transcription suppresser (pGREMEn) and a full-length murine c-myb cDNA sequence. Induced expression of the dominant negative construct was associated with a G1 cell cycle arrest and a failure to increase late G1 intracellular calcium levels. Similar expression studies in mouse embryonic fibroblasts derived from the c-myb knockout mouse have demonstrated lower baseline [Ca2+]i levels than in normal mice fibroblasts that were not further lowered by MEn expression. We conclude that regulation of calcium homeostasis and cell cycle progression via myb-dependent transcription may play an important role in cells not possessing detectable levels of c-myb protein.
Bein
K
K
Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, USA.
Husain
M
M
Ware
J A
JA
Mucenski
M L
ML
Rosenberg
R D
RD
Simons
M
M
D016475:3T3 Cells; D000818:Animals; D002118:Calcium / Q000378:metabolism; D002453:Cell Cycle / Q000502:physiology*; D002478:Cells, Cultured; D003593:Cytoplasm / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000096:biosynthesis; D004330:Drosophila; D004622:Embryo, Mammalian; D004625:Embryo, Nonmammalian; D005347:Fibroblasts; D006579:Heterozygote; D018398:Homeodomain Proteins / Q000096:biosynthesis; D051379:Mice; D018345:Mice, Knockout; D011518:Proto-Oncogene Proteins / Q000096:biosynthesis / Q000502:physiology*; D020598:Proto-Oncogene Proteins c-myb; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis; D015534:Trans-Activators / Q000096:biosynthesis / Q000502:physiology*; D014157:Transcription Factors; D014158:Transcription, Genetic; D014162:Transfection
D004268:DNA-Binding Proteins; D018398:Homeodomain Proteins; D011518:Proto-Oncogene Proteins; D020598:Proto-Oncogene Proteins c-myb; D011993:Recombinant Fusion Proteins; D015534:Trans-Activators; D014157:Transcription Factors; C106185:engrailed homeobox proteins; D002118:Calcium