Mechanisms of kinesin‐7 CENP‐E in kinetochore–microtubule capture and chromosome alignment during cell division

Abstract

Chromosome congression is essential for faithful chromosome segregation and genomic stability in cell division. Centromere-associated protein E (CENP-E), a plus-end-directed kinesin motor, is required for congression of poleproximal chromosomes in metaphase. CENP-E accumulates at the outer plate of kinetochores and mediates the kinetochore-microtubule capture. CENP-E also transports the chromosomes along spindle microtubules towards the equatorial plate. CENP-E interacts with Bub1-related kinase, Aurora B and core kinetochore components during kinetochore-microtubule attachment. In this review, we introduce the structures and mechanochemistry of kinesin-7 CENP-E. We highlight the complicated interactions between CENP-E and partner proteins during chromosome congression. We summarise the detailed roles and mechanisms of CENP-E in mitosis and meiosis, including the kinetochore-microtubule capture, chromosome congression/alignment in metaphase and the regulation of spindle assembly checkpoint. We also shed a light on the roles of CENP-E in tumourigenesis and CENP-E's specific inhibitors.

BUBR1 Pseudokinase Domain Promotes Kinetochore PP2A-B56 Recruitment, Spindle Checkpoint Silencing, and Chromosome Alignment

“…Whether BUBR1 is a bona fide active kinase is a subject that has generated considerable controversy (Guo et al, 2012;Huang et al, 2019;Mao et al, 2003Mao et al, , 2005Suijkerbuijk et al, 2012a;Yu et al, 2019). While our data are in agreement with the idea that BUBR1 is a pseudokinase, we cannot formally exclude catalytic activity under conditions that we have not explored.…”

PLK1 inhibition exhibits strong anti-tumoral activity in CCND1-driven breast cancer metastases with acquired palbociclib resistance

“…PLK1 inhibitors, including volasertib, have been shown to arrest tumour cells in mitosis, with an increase in the polyploid cell population that lead cancer cells to mitotic death 34 . Accordingly, the increase of histone H3 phosphorylation, which occurs specifically in mitosis, and of CENPE expression, a gene specifically expressed during the G2/M phase 35 , 36 , indicates an increase of mitotic cells in volasertib treated xenografts.…”

The BUBR1 pseudokinase domain promotes efficient kinetochore PP2A-B56 recruitment to regulate spindle checkpoint silencing and chromosome alignment

“…Whether BUBR1 is a bona fide active kinase is a subject that has generated considerable controversy 38, 41–43, 73, 78 . If BUBR1 is indeed inactive as proposed before and as we confirm here, an important question that has not yet been addressed is whether the BUBR1 pseudokinase domain retained some function of the ancient MADBUB kinase domain, or acquired new activity as a result of neofunctionalization, that might explain its conservation during vertebrate evolution.…”