Cell cycle control of Cdc7p kinase activity through regulation of Dbf4p stability

Citation
G. Oshiro et al., Cell cycle control of Cdc7p kinase activity through regulation of Dbf4p stability, MOL CELL B, 19(7), 1999, pp. 4888-4896
Citations number
69
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Molecular Biology & Genetics
Journal title
MOLECULAR AND CELLULAR BIOLOGY
ISSN journal
0270-7306 → ACNP
Volume
19
Issue
7
Year of publication
1999
Pages
4888 - 4896
Database
ISI
SICI code
0270-7306(199907)19:7<4888:CCCOCK>2.0.ZU;2-G
Abstract
In Saccharomyces cerevisiae, the heteromeric kinase complex Cdc7p-Dbf4p pla ys a pivotal role at replication origins in triggering the initiation of DN A replication during the S phase. We have assayed the kinase activity of en dogenous levels of Cdc7p kinase by using a likely physiological target, Mcm 2p, as a substrate. Using this assay, we have confirmed that Cdc7p kinase a ctivity fluctuates during the cell cycle; it is low in the G(1) phase, rise s as cells enter the S phase, and remains high until cells complete mitosis . These changes in kinase activity cannot be accounted for by changes in th e levels of the catalytic subunit Cdc7p, as these levels are constant durin g the cell cycle. However, the fluctuations in kinase activity do correlate with levels of the regulatory subunit Dbf4p. The regulation of Dbf4p level s can be attributed in part to increased degradation of the protein in G(1) cells. This G(1)-phase instability is cdc16 dependent, suggesting a role o f the anaphase-promoting complex in the turnover of Dbf4p. Overexpression o f Dbf4p in the G(1) phase can partially overcome this elevated turnover and lead to an increase in Cdc7p kinase activity. Thus, the regulation of Dbf4 p levels through the control of Dbf4p degradation has an important role in the regulation of Cdc7p kinase activity during the cell cycle.