Appearance of CAD Activity, the Rate-Limiting Enzyme for Pyrimidine Biosynthesis, as B Cells Progress into and through the G1 Stage of the Cell Cycle

CAD is a multifunctional protein which mediates the first three enzymatic steps of pyrimidine biosynthesis. Previous studies have implicated CAD as a cell cycle regulated protein. In the present paper CAD activity is studied as polyclonally stimulated, murine B cells progress through the early stages of the cell cycle. CAD activity is seen to increase in a biphasic manner. The initial increase in activity occurs prior to or as the cells increase CAD mRNA suggesting that post-translational modification of preformed enzyme may account for at least a portion of this initial enhancement. Increases in CAD mRNA occur by 12 hr poststimulation and precede the second, more dramatic increase in B cell CAD activity. Preliminary experiments failed to provide support of a role for IL-4 in regulating the expression of CAD as B cells progress into G1. CAD enzymatic activity does represent, however, a marker for early B cell cycle progression.