The characterization of pregnancy associated plasma protein-E and the identification of an alternative splice variant

We have performed differential display and bioinformatic database mining of the placenta, in an attempt to find novel diagnostic markers of pathologic al pregnancies. We have identified a full-length cDNA encoding the prepropr otein of pregnancy associated plasma protein-E (PAPP-E); a putative metallo protease, of 1790-residues with a putative 21-residue signal peptide. An al ternatively spliced mRNA was found to encode an 826-residue precursor prote in corresponding to the N-terminus of PAPP-E. Both PAPP-E variants were fou nd to be co-expressed abundantly in the placenta and non-pregnant mammary g land with low expression in the kidney, foetal brain and pancreas, Analysis of the predicted proteins suggests that the longer variant be targeted to the nucleus while the shorter variant is secreted extracellularly. Gene str ucture analysis revealed that PAPP-E was encoded on 23 exons on chromosome 1 and its splice variant on the first five same exons. The discovery of the PAPP-E variants will help in the deciphering of the physiology of this new family of metzincins in not only the placenta during pregnancy but also th e mammary gland in breast cancer. The new PAPP-E variants could have the po tential for the diagnosis of pathological pregnancies including trisomies s uch as Down's syndrome. (C) 2001 Harcourt Publishers Ltd.