Phorbol ester-mediated regulation of CD10/neutral endopeptidase transcripts in acute lymphoblastic leukemias.
The cell-surface zinc metalloproteinase CD10/neutral endopeptidase 24.11 (CD10/NEP) hydrolyzes a variety of peptide substrates and regulates related peptide-mediated cellular responses. Because the enzyme functions as part of a peptide regulatory loop, the fact that CD10/NEP itself varies with cellular activation is of considerable interest. In hematopoietic and nonhematopoietic cell types, the levels of CD10/NEP protein and enzymatic activity correlate with transcript abundance. For these reasons, we investigated the regulation of CD10/NEP transcripts in the phorbol ester-treated acute lymphoblastic leukemia cell line, REH. When REH cells are treated with phorbol myristate acetate (PMA), CD10/NEP transcripts rapidly decrease in a labile protein-dependent manner. PMA has a modest effect on CD10/NEP transcription and significantly reduces CD10/NEP mRNA stability. Of note, the predicted secondary structure of the CD10/NEP 3' untranslated region includes several stem loop structures that may affect the stability of CD10/NEP transcripts.
Department of Medicine, Dana-Farber Cancer Institute, Boston, MA 02215, USA.
F
F
Ishimaru
N S
NS
Potter
M A
MA
Shipp
D017398:Alternative Splicing / Q000187:drug effects; D001483:Base Sequence; D003513:Cycloheximide / Q000494:pharmacology; D018076:DNA, Complementary / Q000737:chemistry; D004355:Drug Stability; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D006801:Humans; D008969:Molecular Sequence Data; D015260:Neprilysin / Q000235:genetics*; D009690:Nucleic Acid Conformation; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000201:enzymology*; D012333:RNA, Messenger / Q000378:metabolism*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
D018076:DNA, Complementary; D012333:RNA, Messenger; D003513:Cycloheximide; D015260:Neprilysin; D013755:Tetradecanoylphorbol Acetate