This represents the mitotic checkpoint serine/threonine-protein kinase Bub1. Saccharomyces cerevisiae Bub1 has a paralogue, Mad3, which is also included in this entry. Bub1 forms a complex with Mad1 and Bub3 that is crucial for preventing cell cycle progression into anaphase in the presence of spindle damage [], while Mad3 is a component of the spindle-assembly complex consisting of Mad2, Mad3, Bub3 and Cdc20 []. Mad3 contains a D-box and two KEN- boxes, which function together to mediate Cdc20-Mad3 interaction. Mad3 and an anaphase-promoting complex (APC) substrate, Hsl1, compete for Cdc20 binding in a D-box- and KEN-box-dependent manner [].Similar to its yeast homologues, human Bub1 is a critical component of the mitotic checkpoint that delays the onset of anaphase until all chromosomes have established bipolar attachment to the microtubules. In interphase cells it localises to centrosomes and suppresses centrosome amplification via regulating Plk1 activity []. Mutations in the human Bub1 gene have been linked to cancers [, ].
Proteins containing this domain are checkpoint proteins involved in cell division. This region has been shown to be essential for the binding of Bub1 and Mad3 to Cdc20 [].
This domain is found in checkpoint proteins which are involved in cell division. This region has been shown to be necessary and sufficient for the binding of Mad3 to Bub3 in Saccharomyces cerevisiae. This domain is present in Bub1 which also binds Bub3 [].
This entry represents the C-terminal domain of Shugoshin (Sgo1) kinetochore-attachment proteins. Shugoshin has a conserved coiled-coil N-terminal domain and a highly conserved C-terminal basic region (). Shugoshin is a crucial target of Bub1 kinase that plays a central role in chromosome cohesion during mitosis and meiosis divisions by preventing premature dissociation of cohesin complex from centromeres after prophase, when most of cohesin complex dissociates from chromosomes arms [, ]. Shugoshin is thought to act by protecting Rec8 and Rad21 at the centromeres from separase degradation during anaphase I (during meiosis) so that sister chromatids remain tethered []. Shugoshin also acts as a spindle checkpoint component required for sensing tension between sister chromatids during mitosis, its degradation when they separate preventing cell cycle arrest and chromosome loss in anaphase, a time when sister chromatids are no longer under tension. Human shugoshin is diffusible and mediates kinetochore-driven formation of kinetochore-microtubules during bipolar spindle assembly []. Further, the primary role of shugoshin is to ensure bipolar attachment of kinetochores, and its role in protecting cohesion has co-developed to facilitate this process [].
This entry represents the N-terminal domain of Shugoshin (Sgo1) kinetochore-attachment proteins. Shugoshin has this conserved coiled-coil N-terminal domain and a highly conserved C-terminal basic region ().Shugoshin is a crucial target of Bub1 kinase that plays a central role in chromosome cohesion during mitosis and meiosis divisions by preventing premature dissociation of cohesin complex from centromeres after prophase, when most of cohesin complex dissociates from chromosomes arms [, ]. Shugoshin is thought to act by protecting Rec8 and Rad21 at the centromeres from separase degradation during anaphase I (during meiosis) so that sister chromatids remain tethered []. Shugoshin also acts as a spindle checkpoint component required for sensing tension between sister chromatids during mitosis, its degradation when they separate preventing cell cycle arrest and chromosome loss in anaphase, a time when sister chromatids are no longer under tension. Human shugoshin is diffusible and mediates kinetochore-driven formation of kinetochore-microtubules during bipolar spindle assembly []. Further, the primary role of shugoshin is to ensure bipolar attachment of kinetochores, and its role in protecting cohesion has co-developed to facilitate this process [].
