Home | Help | Feedback | Subscriptions | Archive | Search | Table of Contents

This Article Full Text (PDF, 1003K) Alert me when this article is cited Services Email this article Similar articles in this journal Alert me to new content in the JCB Download to citation manager Citing Articles Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Katsnelson, A. Search for Related Content PubMed Articles by Katsnelson, A. Social Bookmarking                            What's this?

Checkpoint yin and yang

Ubiquitin flips the switch for spindle checkpoint inactivation, according to a pair of studies by Sashank Reddy, Marc Kirschner, and colleagues and by Frank Stegmeier, Stephen Elledge (Harvard Medical School, Boston, MA), and colleagues.

The checkpoint stands guard over mitosis to ensure accurate chromosome segregation. While the spindle takes time to assemble, two checkpoint proteins bind tightly to Cdc20 to keep it from activating the anaphase-promoting complex (APC). The checkpoint stays on as long as it senses that kinetochores are still unattached.

The researchers found that flooding the system with UbcH10, which ubiquitinates APC, or p31^comet, a protein previously implicated in checkpoint inactivation, caused cells to crash through the checkpoint. These proteins promoted APC-dependent ubiquitination of Cdc20, which pried it from the checkpoint proteins' grip and released the brake on anaphase.

An RNAi screen in the Elledge lab uncovered a deubiquitinating enzyme, called USP44, that provides the opposing force to keep the checkpoint on. High levels of USP44 caused cells to arrest in mitosis. Without it, cells divided rampantly with chromosome segregation errors.

These opposing forces determine the ultimate level of Cdc20 ubiquitination. Only when Cdc20 is sufficiently ubiquitinated can anaphase procede. Many tumors have elevated levels of UbcH10, which might push them prematurely into anaphase.

References:

Reddy, S.K., et al. 2007. Nature. 446:921–925.[CrossRef][Medline]

Stegmeier, F., et al. 2007. Nature. 446:876–881.[CrossRef][Medline]

Alla Katsnelson

akatsnelson{at}gmail.com

CiteULike    Complore    Connotea    Del.icio.us    Digg    Facebook    Reddit    Technorati    Twitter    What's this?

This Article Full Text (PDF, 1003K) Alert me when this article is cited Services Email this article Similar articles in this journal Alert me to new content in the JCB Download to citation manager Citing Articles Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Katsnelson, A. Search for Related Content PubMed Articles by Katsnelson, A. Social Bookmarking                            What's this?