High impact information on CIN8

• For S. cerevisiae cells, the assembly of a bipolar mitotic spindle requires the action of either Cin8p or Kip1p, gene products related to the mechanochemical enzyme kinesin [1].
• Instead, the checkpoint deficiency leads to deregulation of microtubule-associated proteins Cin8 and Stu2, which, in the absence of both chromosome cohesion and bipolar attachment of kinetochores to microtubules, induce untimely spindle elongation, causing premature chromosome separation [2].
• In addition, we found that yeast cell viability could be supported by as few as two microtubule-based motors: the BimC-type kinesin Cin8p, required for spindle structure, paired with either Kar3p or Kip3p, required for both spindle structure and positioning [3].
• KIP1 and CIN8 are functionally redundant: double mutants arrested in mitosis whereas the single mutants did not [4].
• Cin8p was observed to be a component of the mitotic spindle, colocalizing with the microtubules that lie between the poles [5].

Biological context of CIN8

• These mutations also suppressed the inviability associated with the cin8-delta kip1-delta genotype, a property not shared by a deletion of KAR3 [6].
• Two Saccharomyces cerevisiae genes, CIN8 and KIP1 (a.k.a. CIN9), were identified by their requirement for normal chromosome segregation [5].
• A preanaphase spindle collapse phenotype of cin8 kip1 mutants, previously shown to involve Kar3p, is markedly delayed when microtubule depolymerization is inhibited by the tub2-150 mutation [7].
• Cin8p and Kip1p are also required to prevent an inward spindle collapse prior to anaphase [8].
• Kip1p and Cin8p, which are kinesin-5/BimC family members, cluster kinetochores into their characteristic bilobed metaphase configuration [9].

Anatomical context of CIN8

• The microtubule organizing centers of arrested cells were duplicated but unseparated, indicating that KIP1 or CIN8 is required for mitotic spindle assembly [4].
• Since ectopic expression of proteolysis-resistant Cin8, Kip1 or Ase1 is sufficient for SPB separation even in the absence of Cdc28-Clb activity, we suggest that stabilization of these mechanical force-generating proteins is the predominant role of Cdc28-Clb in centrosome separation [10].
• These include genes whose products act in two spindle motor pathways that overlap in function with Cin8p, the kinesin-related Kip1p pathway and the cytoplasmic dynein pathway [11].
• We report that cin8 mutants are sensitive to the cell wall disrupting agents calcofluor white and SDS [12].

Associations of CIN8 with chemical compounds

• We created a recombinant form of CIN8 that fused the biotin carrying polypeptide from yeast pyruvate carboxylase to the carboxyl terminus of Cin8p [13].
• The N-end rule pathway is required for import of histidine in yeast lacking the kinesin-like protein Cin8p [14].
• Sorbitol could not alleviate the sensitivity of cin8 mutants to calcofluor and SDS [12].

Regulatory relationships of CIN8

• Excess Kar3p has a stronger inhibitory effect on the growth of cin8 kip1 mutants and can completely block anaphase spindle elongation in these cells [8].

Other interactions of CIN8

• KAR3 encodes a distinct kinesin-related protein whose action antagonizes Cin8p/Kip1p function [6].
• Furthermore, we demonstrate that double mutants, defective for SLC1 and the kinesin-related CIN8 genes are non-lethal [15].
• Loss of function of Cin8p (a yeast kinesin-like motor protein) in the absence of either Kip1p (a motor of the same family) or Dyn1p (the dynein heavy chain) is lethal [12].
• The kinesin-related Cin8p and cytoplasmic dynein are microtubule-associated motor proteins required for anaphase spindle elongation in the yeast Saccharomyces cerevisiae [16].

References