Phosphorylation and activation of Bub1 on unattached chromosomes facilitate the spindle checkpoint

AUTOR(ES)

Chen, Rey-Huei

FONTE

Nature Publishing Group

RESUMO

The spindle checkpoint inhibits anaphase until all kinetochores have attached properly to spindle microtubules. The protein kinase Bub1 is an essential checkpoint component that resides at kinetochores during mitosis. It is shown herein that Xenopus Bub1 becomes hyperphosphorylated and the kinase is activated on unattached chromosomes. MAP kinase (MAPK) contributes to this phosphorylation, as inhibiting MAPK or altering MAPK consensus sites in Bub1 to alanine or valine (Bub15AV) abolishes the phosphorylation and activation on chromosomes. Both Bub1 and Bub15AV support the checkpoint under an optimal condition for spindle checkpoint activation. However, Bub1, but not Bub15AV, supports the checkpoint at a relatively low concentration of nuclei or the microtubule inhibitor nocodazole. Similar to Bub15AV, Bub1 without the kinase domain (Bub1ΔKD) is also partially compromised in its checkpoint function and in its ability to recruit other checkpoint proteins to kinetochores. This study suggests that activation of Bub1 at kinetochores enhances the efficiency of the spindle checkpoint and is probably important in maintaining the checkpoint toward late prometaphase when the cell contains only a few or a single unattached kinetochore.

Documentos Relacionados

• Simian virus 40 large T antigen targets the spindle assembly checkpoint protein Bub1
• The Saccharomyces cerevisiae checkpoint gene BUB1 encodes a novel protein kinase.
• Function of Cdc2p-dependent Bub1p phosphorylation and Bub1p kinase activity in the mitotic and meiotic spindle checkpoint
• Retention of the Bub3 checkpoint protein on lagging chromosomes
• Bub1p Kinase Activates the Saccharomyces cerevisiae Spindle Assembly Checkpoint