Down-regulation of a serine protease, myeloblastin, causes growth arrest and differentiation of promyelocytic leukemia cells.
Cells from the human leukemia cell line HL-60 undergo terminal differentiation when exposed to inducing agents. Differentiation of these cells is always accompanied by withdrawal from the cell cycle. Here we describe the isolation of a cDNA encoding a novel serine protease that is present in HL-60 cells and is down-regulated during induced differentiation of these cells. We have named this protease myeloblastin. Down-regulation of myeloblastin mRNA occurs with both monocytic and granulocytic inducers. Myeloblastin mRNA is undetectable in fully differentiated HL-60 cells as well as in human peripheral blood monocytes. We found that regulation of myeloblastin mRNA in HL-60 cells is serum dependent. Inhibition of myeloblastin expression by an antisense oligodeoxynucleotide inhibits proliferation and induces differentiation of promyelocyte-like leukemia cells.
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Department of Physiology and Cellular Biophysics, Columbia University College of Physicians and Surgeons, New York, New York 10032.
Raynal
M C
MC
Solomon
D H
DH
Darzynkiewicz
Z
Z
Cayre
Y E
YE
D000595:Amino Acid Sequence; D001483:Base Sequence; D002454:Cell Differentiation / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D003470:Culture Media; D004273:DNA, Neoplasm / Q000235:genetics; D015971:Gene Expression Regulation, Enzymologic; D005796:Genes; D006801:Humans; D015473:Leukemia, Promyelocytic, Acute; D008969:Molecular Sequence Data; D053146:Myeloblastin; D009838:Oligodeoxyribonucleotides / Q000494:pharmacology; D012333:RNA, Messenger / Q000235:genetics; D012697:Serine Endopeptidases / Q000096:biosynthesis / Q000235:genetics*; D014158:Transcription, Genetic; D014407:Tumor Cells, Cultured / Q000166:cytology / Q000187:drug effects / Q000201:enzymology*
D003470:Culture Media; D004273:DNA, Neoplasm; D009838:Oligodeoxyribonucleotides; D012333:RNA, Messenger; D012697:Serine Endopeptidases; D053146:Myeloblastin