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Phosphorylation and activation of Bub1 on unattached chromosomes facilitate the spindle checkpoint
Author(s) -
Chen ReyHuei
Publication year - 2004
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1038/sj.emboj.7600308
Subject(s) - bub1 , spindle checkpoint , kinetochore , microbiology and biotechnology , prometaphase , g2 m dna damage checkpoint , anaphase promoting complex , cell cycle checkpoint , biology , chemistry , cell cycle , biochemistry , cell , gene , chromosome
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 (Bub1 5AV ) abolishes the phosphorylation and activation on chromosomes. Both Bub1 and Bub1 5AV support the checkpoint under an optimal condition for spindle checkpoint activation. However, Bub1, but not Bub1 5AV , supports the checkpoint at a relatively low concentration of nuclei or the microtubule inhibitor nocodazole. Similar to Bub1 5AV , Bub1 without the kinase domain (Bub1 ΔKD ) 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.