Ecto-5'-nucleotidase (CD73): genomic cloning and characterization of regions upstream of the translation start site.

Abstract

Ecto-5’-nucleotidase (5’-NT, CD73) catalyzes the dephosphorylation of ribo- and deoxyribonucleoside monophosphates to the corresponding nucleosides, which are then able to enter cells via facilitated diffusion and participate in purine salvage or are catabolized to uric acid. 5’-NT is expressed on a variety of cell types including lymphocytes, transitional cell mucosa, the basal layer of nonkeratinizing squamous epithelium, and the stromal cells of human breast cancers.1 There are at least three examples where 5’-NT and adenosine deaminase (ADA), a second purine salvage pathway enzyme, are expressed in a reciprocal fashion in adjacent layers of cells: the thymus2, 3, the developing mouse embryo4, and the retina5. Additionally, an examination of the specific cell types which express 5’-NT and ADA in murine gastrointestinal tract tissues revealed that ADA was localized to the superficial layers of the squamous epithelium of the tongue and esophagus6, while 5’-NT was found in the basal layer of human oral mucosa, a similar tissue1. Because 5’-NT and ADA are expressed in a reciprocal manner in some tissues, we hypothesize that these molecules may share genetic elements which regulate their expression in a coordinated manner. In order to evaluate this hypothesis extensive characterization of the 5’-NT promoter region is necessary. This initial characterization will create a framework upon which additional experiments can directly assess the interactions between factors which regulate the expression of 5’-NT and ADA.