APPEARANCE OF CAD ACTIVITY, THE RATE-LIMITING ENZYME FOR PYRIMIDINE BIOSYNTHESIS, AS B-CELLS PROGRESS INTO AND THROUGH THE G(1) STAGE OF THE CELL-CYCLE

CAD is a multifunctional protein which mediates the first three enzyma tic steps of pyrimidine biosynthesis. Previous studies have implicated CAD as a cell cycle regulated protein. In the present paper CAD activ ity is studied as polyclonally stimulated, murine B cells progress thr ough the early stages of the cell cycle. CAD activity is seen to incre ase in a biphasic manner. The initial increase in activity occurs prio r to or as the cells increase CAD mRNA suggesting that posttranslation al modification of preformed enzyme may account for at least a portion of this initial enhancement. Increases in CAD mRNA occur by 12 hr pos tstimulation and precede the second, more dramatic increase in B cell CAD activity. Preliminary experiments failed to provide support of a r ole for IL-4 in regulating the expression of CAD as B cells progress i nto G(1). CAD enzymatic activity does represent, however, a marker for early B cell cycle progression. (C) 1994 Academic Press, Inc.