bis_104_cell_cycle_fall_08

bis_104_cell_cycle_fall_08 - BIS 104 CONTROL OF CELL CYCLE...

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BIS 104 CONTROL OF CELL CYCLE A. Regulation of cyclin-dependent kinases (Cdks), the engines that drive the cell cycle. 1. Cyclin protein concentration Different cyclin genes are expressed at different times during the cycle. There are S-phase cyclins and M-phase cyclins (figs 14.5 and 14.8) 2. Cdk phosphorylation state Binding of cyclin to kinase is required but not sufficient to activate the kinase Threonine-161 on kinase is phosphorylated by Cdk-activating kinase (CAK) Tyrosine-15 on kinase is phosphorylated by wee-1 Complexes are now inactive (fig. 14.6) Phosphatase cdc-25 removes phosphate from tyrosine-15 to activate the complex 3. Cdk inhibitors 6 – 10 different proteins have been identified that bind directly to Cdk / cyclin complexes to inactivate (e.g., proteins p21 and p27). These are the “brakes’ on the engine and they prevent inappropriate entry into S-phase if DNA is damaged. 4. Controlled proteolysis
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Cyclin levels are determined by a balance between newly synthesized protein and degradation.
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