Finding degradation at the checkpoint

杨柳

When the mitotic apparatus is disturbed by agents such as nocodazole, mitotic checkpoints delay mitosis to avert disaster. Defects in the anaphase-onset checkpoint are rarely seen in cancers, but defects in the G2/M (prophase) checkpoint are present in multiple tumor cell lines. Now, on page 249, Kang et al. report that the recently identified G2/M checkpoint protein Chfr is a ubiquitin ligase that promotes the degradation of a regulatory protein. In addition to describing a novel cell cycle checkpoint mechanism, the authors have developed an experimental system that should be useful in future studies on Chfr.
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Kang et al. found that Chfr can ubiquitinate itself and other proteins in vitro and in vivo. In a Xenopus egg extract system, recombinant Chfr delays the activation of the kinase Cdc2 during the G2/M transition. Using this system,the authors determined that Chfr ubiquitinates polo-like kinase 1 (Plk1), leading to its degradation. Plk1 ordinarily triggers a cascade that leads to Cdc2 dephosphorylation and mitosis, so its degradation leaves Cdc2 phosphorylated and halts progression into mitosis. Future work on the cell-free system should help uncover the mechanisms that link Chfr activity to mitotic stresses, such as microtubule defects.(Chfr can ubiquitinate itself.)