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Carbamoyl phosphate synthetase-aspartate carbamoyltransferase-dihydroorotase (CAD) is a multifunctional protein that initiates and regulates mammalian de novo pyrimidine biosynthesis (1). This trifunctional protein which is associated with the enzymatic activities of the first 3 enzymes in the 6-step pathway of pyrimidine biosynthesis is the rate-limiting step in the de novo pyrimidine synthetic pathway (2). Although most of the CAD protein in the cell is cytosolic, phosphorylation at threonine 456 localizes the protein to the nucleus (3). While MAPK and EGF phosphorylate CAD at threonine 456, MAPK and c-myc have been found to induce over-expression of CAD (4-5).
