A novel aspartyl proteinase from apocrine epithelia and breast tumors

GCDFP-15 gross cystic disease fluid protein, 15 kDa is a secretory marker o f apocrine differentiation in breast carcinoma. In human breast cancer cell lines, gene expression is regulated by hormones, including androgens and p rolactin. The protein is also known under different names in different body fluids such as gp17 in seminal plasma. GCDFP-15/gp17 is a ligand of CD4 an d is a potent inhibitor of T-cell apoptosis induced by sequential CD4/T-cel l receptor triggering. We now report that GCDFP-15/gp17 is a protease exhib iting structural properties relating it to the aspartyl proteinase superfam ily. Unexpectedly, GCDFP-15/gp17 appears to be related to the retroviral me mbers rather than to the known cellular members of this class. Site-specifi c mutagenesis of Asp(22) (predicted to be catalytically important for the a ctive site) and pepstatin A inhibition confirmed that the protein is an asp artic-type protease. We also show that, among the substrates tested, GCDFP- 15/gp17 is specific for fibronectin. The study of GCDFP-15/gp17-mediated pr oteolysis may provide a handle to understand phenomena as diverse as mammar y tumor progression and fertilization.