Disease relevance of BIR1

• Yeast two-hybrid and genetic interaction screens indicate that Bir1p, a yeast protein containing phylogenetically conserved antiapoptotic repeat domains called baculovirus inhibitor of apoptosis repeats (BIRs), is involved in chromosome segregation events [1].

High impact information on BIR1

• A Bir1-Sli15 complex connects centromeres to microtubules and is required to sense kinetochore tension [2].
• Elimination of the linkage between centromeres and microtubules mediated by Bir1-Sli15 phenocopies mutations that selectively cripple Ipl1 kinase activation [2].
• Using an in vitro approach based on the sequence-specific budding yeast centromere, we identified a complex of the chromosomal passenger proteins Bir1 and Sli15 (Survivin and INCENP) that links centromeres to microtubules [2].
• We find that lysine to arginine mutations that eliminate the sumoylation of Ndc10 cause chromosome instability, mislocalization of Ndc10 from the mitotic spindle, abnormal anaphase spindles, and a loss of Bir1 sumoylation [3].
• Consistent with this possibility, we find that CBF3 interacts with Bir1p, the homologue of the passenger protein Survivin [4].

Biological context of BIR1

• In addition, deletion of BIR1 is synthetically lethal with deletion of CBF1 or CTF19, genes specifying two other components of the yeast kinetochore [1].
• Yeast cells deleted of BIR1 have a chromosome-loss phenotype, which can be completely rescued by elevating NDC10 dosage [1].
• Participation of Bir1p, a member of the inhibitor of apoptosis family, in yeast chromosome segregation events [1].
• Under starvation conditions, however, BIR1 mutant diploids formed spores inefficiently, instead undergoing pseudohyphal differentiation [5].
• In rich medium, BIR1 mutant S. cerevisiae underwent normal vegetative growth and mitosis [5].

Anatomical context of BIR1

• Finally, BIR1 heterozygous mutants exhibited grossly altered cell morphology with misshapen or abnormally long buds connected to an unusually large mother cell [6].

Associations of BIR1 with chemical compounds

• Here, we show that Bir1p is a substrate for Nma111p, which is the homologue of the human pro-apoptotic serine protease Omi/HtrA2 and which is known to mediate apoptosis in yeast [7].
• This linkage does not require Ipl1/Aurora B kinase, whose targeting and activation are controlled by Bir1 and Sli15 [2].

Physical interactions of BIR1

• In the two-hybrid screen, Bir1p specifically interacts with Ndc10p, an essential component of the yeast kinetochore [1].

Regulatory relationships of BIR1

• Mutation of all nine CDK consensus sites in the middle region of Bir1 significantly decreased the level of phosphorylation and blocked localization of Ndc10 to the spindle at anaphase [8].

Other interactions of BIR1

• Although Bir1p carries two BIR motifs in the N-terminal region, the C-terminal third of the protein is sufficient to provide strong interaction with Ndc10p and moderate interaction with Skp1p, another essential component of the yeast kinetochore [1].
• Therefore, Bir1p, like its closest metazoan homologues deterin and survivin, has dual functions: it participates in chromosome segregation events and cytokinesis and exhibits anti-apoptotic activity [7].

Analytical, diagnostic and therapeutic context of BIR1

• Moreover, immunoprecipitation of Ndc10 with Bir1 was dependent on phosphorylation [8].

References