Promoter regulatory motifs involved in c-mpl gene expression induced by PMA.
Phorbol-12-myristate-13-acetate (PMA) significantly elevated c-mpl promoter activity and the protein kinase C (PKC) inhibitors GF 109203, H7 and calphostin C conspicuously reduced the steady level of the activity. Destruction of the -107Sp1 and the -57Sp1 sites in the c-mpl promoter enhancer region resulted in decrease of the promoter activity by 49.6% and 48.2%, respectively, and destruction of -69Ets and -28Ets elements dramatically decreased the activity by 93.4% and 82.6%, respectively, while mutation of -77GATA moderately reduced the activity by 28.6%. We conclude that the expression of the c-mpl gene is modulated by transcription through a PKC-dependent pathway and that Ets elements at -69 and -28 nucleotides in front of the transcription start site are critical that Sp1(-107) and Sp1(-57) are also important and that GATA(-77) is less involved as a positive regulatory element in c-mpl gene expression induced by PMA in CMK cells.
Sunohara
Masataka
M
Department of Anatomy, School of Life Dentistry at Tokyo, The Nippon Dental University, 1-9-20 Fujimi, Chiyoda-ku, Tokyo 102-8159, Japan. ma-suno@tky.ndu.ac.jp
Morikawa
Shigeru
S
Sato
Takeyuki
T
Miyado
Mami
M
Sato
Iwao
I
Sato
Toru
T
Fuse
Akira
A
D001665:Binding Sites; D002460:Cell Line; D004742:Enhancer Elements, Genetic; D006801:Humans; D017354:Point Mutation; D011401:Promoter Regions, Genetic; D011493:Protein Kinase C / Q000037:antagonists & inhibitors; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D050783:Proto-Oncogene Proteins c-ets / Q000378:metabolism; D053628:Receptors, Thrombopoietin / Q000235:genetics*; D017384:Sequence Deletion; D016329:Sp1 Transcription Factor / Q000378:metabolism; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology*; D015533:Transcriptional Activation
D047428:Protein Kinase Inhibitors; D050783:Proto-Oncogene Proteins c-ets; D053628:Receptors, Thrombopoietin; D016329:Sp1 Transcription Factor; C082218:MPL protein, human; D011493:Protein Kinase C; D013755:Tetradecanoylphorbol Acetate