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The type 2 CD10/neutral endopeptidase 24.11 promoter: functional
characterization and tissue-specific regulation by CBF/NF-Y isoforms
F Ishimaru, B Mari and MA Shipp
Department of Medicine, Dana-Farber Cancer Institute and Harvard Medical
School, Boston, MA 02115, USA.
The cell surface zinc metalloproteinase CD10/neutral endopeptidase 24.11
([NEP] neprilysin) functions as part of a regulatory loop to control local
concentrations of peptide substrates and associated peptide-mediated signal
transduction. The physiologic role of the enzyme depends on available
substrates in specific organs and cell types. Although CD10/NEP is
expressed on a restricted subset of normal and malignant lymphoid
progenitors, the enzyme is also expressed by a variety of epithelial cells.
To explore the mechanism of tissue- specific expression of this regulatory
enzyme, we characterized the major (type 2) CD10/NEP promoter and
identified three functionally active transcription factor binding sites
(regions I to III). CBF/NF-Y binds to the inverted CCAAT box in region I,
whereas a second positive and a third negative factor bind to regions II
and III, respectively. Although region I is required for maximal
CD10/NEP-driven luciferase activity in the examined epithelial cell lines,
this region is not required for maximal activity in the evaluated lymphoid
cell lines. The apparent tissue-specific differences in requirements for
region I (and CBF/NF-Y) are of particular interest because lymphoid and
epithelial cells express alternatively spliced versions of CBF/NF-Y that
differ in biologic activity.
Volume 89,
Issue 11,
pp. 4136-4145,
06/01/1997
Copyright © 1997 by The American Society of Hematology
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