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 funct ions as part of a peptide regulatory loop, the fact that CD10/NEP itse lf varies with cellular activation is of considerable interest. In hem atopoietic and nonhematopoietic cell types, the levels of CD10/NEP pro tein and enzymatic activity correlate with transcript abundance. For t hese reasons, we investigated the regulation of CD10/NEP transcripts i n the phorbol ester-treated acute lymphoblastic leukemia cell line, RE H. When REH cells are treated with phorbol myristate acetate (PMA), CD 10/NEP transcripts rapidly decrease in a labile protein-dependent mann er. PMA has a modest effect on CD10/NEP transcription and significantl y reduces CD10/NEP mRNA stability. Of note, the predicted secondary st ructure of the CD10/NEP 3' untranslated region includes several stem l oop structures that may affect the stability of CD10/NEP transcripts.