Identification of a phorbol ester responsive region in the myeloid-specific promoter of the c-fgr proto-oncogene.
Expression of the c-fgr proto-oncogene is activated during differentiation of myeloid cells. We used a luciferase reporter assay to identify sequences that regulate c-fgr gene transcription during differentiation of human U937 promonocytic cells, induced by phorbol 12-myristate 13-acetate (PMA) or by tumour necrosis factor-alpha (TNF-alpha) and 1,25-dihydroxycholecalciferol (1,25-DHCC). We found that the region from nucleotides -344 to -116, with respect to the transcriptional start site, is required for basal activity of the c-fgr promoter in U937 cells, and that the region from nucleotides -1211 to -752 is responsive to PMA. No sequence elements responsive to TNF-alpha and 1,25-DHCC were found, suggesting that these agents induce c-fgr mRNA accumulation by a mechanism differing from that mediating the effects of PMA.
Kefalas
P
P
Department of Molecular Pathology, University College London Medical School, UK.
Brown
T R
TR
Katz
D R
DR
Brickell
P M
PM
D001853:Bone Marrow / Q000378:metabolism*; D002117:Calcitriol / Q000494:pharmacology; D003001:Cloning, Molecular; D006801:Humans; D010957:Plasmids; D011401:Promoter Regions, Genetic; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology*; D015533:Transcriptional Activation / Q000187:drug effects; D014407:Tumor Cells, Cultured; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D019061:src-Family Kinases
C000715470:MAS1 protein, human; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins; D014409:Tumor Necrosis Factor-alpha; C053102:proto-oncogene proteins c-fgr; D019061:src-Family Kinases; D002117:Calcitriol; D013755:Tetradecanoylphorbol Acetate