Interphase APC/C–Cdc20 inhibition by cyclin A2–Cdk2 ensures efficient mitotic entry

Interphase APC/C–Cdc20 inhibition by cyclin A2–Cdk2 ensures efficient mitotic entry

Proper cell-cycle progression requires tight temporal control of the Anaphase Promoting Complex/Cyclosome (APC/C), a large ubiquitin ligase that is activated by one of two co-activators, Cdh1 or Cdc20. APC/C and Cdc20 are already present during interphase but APC/C-Cdc20 regulation during this window of the cell cycle, if any, is unknown. Here we show that cyclin A2-Cdk2 binds and phosphorylate...

A Two-Step Inactivation Mechanism of Myt1 Ensures CDK1/Cyclin B Activation and Meiosis I Entry

Activation of CDK1 is essential for M-phase entry both in mitosis and meiosis. G2-arrested oocytes contain a pool of CDK1/cyclin B complexes that are maintained inactive because of the phosphorylation of CDK1 on Thr14 and Tyr15 by the Wee1 family protein kinase Myt1, whose inhibition suffices to induce meiosis I entry [1-5]. CDK1/XRINGO and p90Rsk can both phosphorylate and downregulate Myt1 ac...

The Mitotic Index and Interphase Processes

Reversal of chlorsulfuron-induced inhibition of mitotic entry by isoleucine and valine.

Pea (Pisum sativum L. cv Alaska) root tips were excised and cultured aseptically in White's medium. Cultures were treated immediately or after a 24 hour equilibration time with 28 nanomolar chlorsulfuron plus isoleucine and valine (each 0.1 millimolar), isoleucine and valine, or untreated. The percentage of mitotic figures in untreated control roots sampled immediately after excision showed a t...

Forced mitotic entry of S-phase cells as a therapeutic strategy induced by inhibition of WEE1.

Inhibition of the protein kinase WEE1 synergizes with chemotherapy in preclinical models and WEE1 inhibitors are being explored as potential cancer therapies. Here, we investigate the mechanism that underlies this synergy. We show that WEE1 inhibition forces S-phase-arrested cells directly into mitosis without completing DNA synthesis, resulting in highly abnormal mitoses characterized by dispe...