Coordinated synthesis and degradation of cdc2 in the mammalian cell cycle

Abstract

The product of the cdc2 gene (cdc2 or ), the catalytic subunit of M phase-promoting factor ), is held at a constant steady-state level throughout the cle. In this report, we show that the constant concenis maintained by a coordinated regulation of protein is and degradation. At the end of each mitosis, cdc2 ription is shut off, and the mRNA is rapidly degraded. A activation of cdc2 gene transcription occurs every round cell cycle at the G1/S transition, in a growth factor-lent manner. The increase in mRNA correlates with the ulation of newly synthesized cdc2 during S and G2 s. At the onset of mitosis, the translation of cdc2 mRNA off. During G1 phase, the cdc2 protein has a relatively olf-life of 18 hr, so cdc2 made in the previous cell cycle ained. Once synthesis is activated at G1/S, a concurmechanism of degradation is activated, and the protein e is reduced to 7.5 hr. By the end of interphase, new cdc2 s for 75-85% of the total cdc2 pool. In addition, we that >75% of the new cdc2 complexes with cyclin, ting that a majority of the new cdc2 functions as MPF.