Coordinated synthesis and degradation of cdc2 in the mammalian cell cycle.
The product of the cdc2 gene (cdc2 or p34cdc2), the catalytic subunit of M phase-promoting factor (MPF), is held at a constant steady-state level throughout the cell cycle. In this report, we show that the constant concentration is maintained by a coordinated regulation of protein synthesis and degradation. At the end of each mitosis, cdc2 transcription is shut off, and the mRNA is rapidly degraded. A 12-fold activation of cdc2 gene transcription occurs every round of the cell cycle at the G1/S transition, in a growth factor-dependent manner. The increase in mRNA correlates with the accumulation of newly synthesized cdc2 during S and G2 phases. At the onset of mitosis, the translation of cdc2 mRNA is shut off. During G1 phase, the cdc2 protein has a relatively long half-life of 18 hr, so cdc2 made in the previous cell cycle is maintained. Once synthesis is activated at G1/S, a concurrent mechanism of degradation is activated, and the protein half-life is reduced to 7.5 hr. By the end of interphase, new cdc2 accounts for 75-85% of the total cdc2 pool. In addition, we show that greater than 75% of the new cdc2 complexes with cyclin, suggesting that a majority of the new cdc2 functions as MPF.
Department of Biology, University of California, San Diego, La Jolla 92093.
P J
PJ
Welch
J Y
JY
Wang
D016475:3T3 Cells; D000818:Animals; D015153:Blotting, Western; D016203:CDC2 Protein Kinase / Q000235:genetics / Q000378:metabolism*; D002453:Cell Cycle; D002478:Cells, Cultured; D016213:Cyclins / Q000378:metabolism; D005347:Fibroblasts; D015870:Gene Expression; D006367:HeLa Cells; D006801:Humans; D066298:In Vitro Techniques; D046911:Macromolecular Substances; D000090204:Mesothelin; D051379:Mice; D019000:Phosphotyrosine; D012333:RNA, Messenger / Q000235:genetics; D014158:Transcription, Genetic; D014443:Tyrosine / Q000031:analogs & derivatives / Q000378:metabolism
D016213:Cyclins; D046911:Macromolecular Substances; C000715528:Msln protein, mouse; D012333:RNA, Messenger; D019000:Phosphotyrosine; D014443:Tyrosine; D016203:CDC2 Protein Kinase; D000090204:Mesothelin