High impact information on BUB1

• Establishment of this Sgo1-binding domain requires the 120-base-pair (bp) core centromere, the kinetochore component Bub1, and the meiosis-specific factor Spo13 [1].
• Requirement of Skp1-Bub1 interaction for kinetochore-mediated activation of the spindle checkpoint [2].
• The Skp1's interaction with Bub1 is required for the mitotic delay induced by kinetochore tension defects, but not for the arrest induced by spindle depolymerization, kinetochore assembly defects, or Mps1 overexpression [2].
• We propose that the Skp1-Bub1 interaction is important for transmitting a signal to the spindle checkpoint pathway when insufficient tension is present at kinetochores [2].
• Components of the spindle checkpoint include the mitotic arrest defective (MAD) genes MAD1-3, and the budding uninhibited by benzimidazole (BUB) genes BUB1 and BUB3 [3].

Biological context of BUB1

• In the presence of spindle damage, BUB1 is required to prevent cell cycle progression into anaphase [4].
• Finally, overexpression of wild-type BUB1 or MAD3 genes leads to chromosome instability [5].
• A 156-amino acid fragment of Bub1p functions in Bub3p binding and in kinetochore localization by one-hybrid assay [5].
• In vitro experiments confirmed that Bub1 possesses kinase activity; Bub1 was able to autophosphorylate and to catalyze phosphorylation of Bub3 [6].
• We show that Bub1 also has a crucial role in normal, unperturbed mitoses [7].

Anatomical context of BUB1

• In addition, overproduced Bub1 was found to localize to the cell nucleus [6].
• Disruption of astral microtubule contact with the cell cortex activates a Bub1, Bub3, and Mad3-dependent checkpoint in fission yeast [8].
• Bub1 is activated by the protein kinase p90(Rsk) during Xenopus oocyte maturation [9].

Associations of BUB1 with chemical compounds

• In yeast, the serine/threonine protein kinase Bub1 and the WD-repeat protein Bub3 are elements of a signal transduction cascade that regulates the kinetochore attachment checkpoint [9].

Physical interactions of BUB1

• Analysis of this activity indicates that the Bub3p-binding domain of Bub1p contributes to this phenotype through disruption of checkpoint activity as well as through introduction of kinetochore or spindle damage [5].

Other interactions of BUB1

• This suggests that the Bub1p and Mps1p kinases act together at an early step in generating the spindle damage signal [4].
• The bub1-A78V mutant is of particular interest because it produces a wild-type amount of protein that is mutated in the conserved but uncharacterized Mad3-like region of Bub1p [10].
• In budding yeast, the Mad1, 2, 3, and Bub1, 2, 3 proteins mediate this arrest [11].
• We find that three genes (MAD2, BUB1, and BUB2) that are required for the spindle assembly checkpoint in budding yeast (defined by antimicrotubule drug-induced arrest or delay) are also required in the establishment and/or maintenance of kinetochore-induced delays [12].

Analytical, diagnostic and therapeutic context of BUB1

• Sequence analysis of BUB1 revealed a domain with similarity to protein kinases [6].
• Genetic evidence was obtained suggesting that Bub1 and Bub3 are mutually dependent for function, and immunoprecipitation experiments demonstrated a physical association between the two [6].
• In Xenopus oocytes, Bub1 is localized to kinetochores during both meiosis I and meiosis II, and the electrophoretic mobility of Bub1 upon SDS-PAGE decreases during meiosis I, reflecting phosphorylation and activation of the enzyme [9].

References