Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.6.4.4 (kinesin)
 5,033 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Cohesins and their regulators are vital for normal chromosome cohesion and segregation. A number of cohesion proteins have also been localized to centrosomes and proposed to function there. We show that RNAi-mediated depletion of factors required for cohesion, including haspin, Sgo1 and Scc1, leads to the generation of multiple acentriolar centrosome-like foci and disruption of spindle structure in mitosis. Live-cell imaging reveals that, in haspin-depleted cells, these effects occur only as defects in chromosome cohesion become manifest, and they require ongoing microtubule dynamics and kinesin-5 (also known as Eg5) activity. Inhibition of topoisomerase II in mitosis, which prevents decatenation and separation of chromatids, circumvents the loss of cohesion and restores integrity of the spindle poles. Although these results do not rule out roles for cohesin proteins at centrosomes, they suggest that when cohesion is compromised, spindle-pole integrity can be disrupted as an indirect consequence of the failure to properly integrate chromosome- and centrosome-initiated pathways for spindle formation.
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PMID:Studies of haspin-depleted cells reveal that spindle-pole integrity in mitosis requires chromosome cohesion. 1991 Apr 98

Shugoshins (Sgo) are conserved proteins that act as protectors of centromeric cohesion and as sensors of tension for the machinery that eliminates improper kinetochore-microtubule attachments. Most vertebrates contain two Sgo proteins, but their specific functions are not always clear. Xenopus laevis Sgo1, XSgo1, protects centromeric cohesin from the prophase dissociation pathway. Here, we report the identification of XSgo2 and show that it does not regulate cohesion. Instead, we find that it participates in bipolar spindle assembly. Both Sgo proteins interact physically with the Chromosomal Passenger Complex (CPC) containing Aurora B, a key regulator of mitosis, but the functional consequences of such interaction are distinct. XSgo1 is required for proper localization of the CPC while XSgo2 positively contributes to its activation and the subsequent phosphorylation of at least one key substrate for bipolar spindle assembly, the microtubule depolymerizing kinesin MCAK (Mitotic Centromere-Associated Kinesin). Thus, the two Xenopus Sgo proteins have non-overlapping functions in chromosome segregation. Our results further suggest that this functional specificity could rely on the association of XSgo1 and XSgo2 with different regulatory subunits of the PP2A complex.
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PMID:Xenopus Shugoshin 2 regulates the spindle assembly pathway mediated by the chromosomal passenger complex. 2227 15