Activation of the fructose 1,6-bisphosphatase gene by 1,25-dihydroxyvitamin D3 during monocytic differentiation.
Cells from the human leukemia cell line HL-60 undergo terminal monocyte-like differentiation after exposure to either the active circulating form of vitamin D3, 1,25-dihydroxyvitamin D3 [1,25-(OH)2D3], or phorbol 12-myristate 13-acetate. Little is known about the genes that regulate monocytic differentiation. Using clonal variant cells of HL-60 origin, we constructed a cDNA library enriched for genes that are induced by 1,25-(OH)2D3. We now report that in HL-60, the fructose 1,6-bisphosphatase (FBPase; D-fructose-1,6-bisphosphate 1-phosphohydrolase, EC 3.1.3.11) gene is activated during 1,25-(OH)2D3-induced monocytic differentiation. This gene encodes two closely related mRNAs; one, activated by 1,25-(OH)2D3 at an early stage of HL-60 differentiation, encodes a protein that has homology to mammalian FBPase, a key enzyme in gluconeogenesis, although it does not exhibit its classical enzymatic activity. A second mRNA is activated by 1,25-(OH)2D3 mainly in peripheral blood monocytes. This mRNA is present in kidney as a unique transcript and encodes a protein with FBPase activity. Our data also show that this FBPase-encoding mRNA can be activated during monocytic maturation since it was detected in human alveolar macrophages.
Solomon
D H
DH
Program in Immunology, Memorial Sloan-Kettering Cancer Center, New York, NY 10021.
Raynal
M C
MC
Tejwani
G A
GA
Cayre
Y E
YE
D000595:Amino Acid Sequence; D001483:Base Sequence; D002117:Calcitriol / Q000494:pharmacology*; D002999:Clone Cells; D006597:Fructose-Bisphosphatase / Q000235:genetics*; D005786:Gene Expression Regulation; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000473:pathology; D008969:Molecular Sequence Data; D009000:Monocytes / Q000187:drug effects*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D006597:Fructose-Bisphosphatase; D002117:Calcitriol; D013755:Tetradecanoylphorbol Acetate