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.