Aurora B kinase

4AF3921220877ENSG00000178999ENSMUSG00000020897Q96GD4O70126NM_001313955NM_001256834NM_001284526NM_004217NM_011496NP_001300882NP_001300883NP_001300884NP_004208NP_035626Aurora B kinase is a protein that functions in the attachment of the mitotic spindle to the centromere. Aurora B kinase is a protein that functions in the attachment of the mitotic spindle to the centromere. Chromosomal segregation during mitosis as well as meiosis is regulated by kinases and phosphatases. The Aurora kinases associate with microtubules during chromosome movement and segregation. Aurora kinase B localizes to microtubules near kinetochores, specifically to the specialized microtubules called K-fibers, and Aurora kinase A (MIM 603072) localizes to centrosomes (Lampson et al., 2004). In cancerous cells, over-expression of these enzymes causes unequal distribution of genetic information, creating aneuploid cells, a hallmark of cancer. In 1998, Aurora kinase B was identified in humans by a polymerase chain reaction screen for kinases that are overexpressed in cancers. In the same year, rat Aurora kinase B was identified in a screen designed to find kinases that altered S. cerevisiae proliferation when overexpressed. The expression and activity of Aurora B are regulated according to the cell cycle. Expression of Aurora B reaches a maximum at the G2-M transition, whereas Aurora B protein is most active during mitosis. Aurora B is a chromosomal passenger protein. Specifically, Aurora B localizes to the chromosomes in prophase, the centromere in prometaphase and metaphase, and the central mitotic spindle in anaphase. This localization has been determined by indirect immunofluorescence in mammalian, C. elegans, and Drosophila cells. A more detailed analysis of Aurora B localization has been carried out in mammalian cells by tagging Aurora B with green fluorescent protein. This analysis showed that the association of Aurora B with centromeres is dynamic (Aurora B at the centromere is constantly exchanging with a pool of cytoplasmic Aurora B). The analysis of tagged Aurora B also suggested that it associates with spindle microtubules during anaphase of mitosis and this association significantly limits its mobility. Finally, a portion of the tagged Aurora B localized to the equatorial cell cortex, having been transported to this location by astral microtubules. Aurora B complexes with three other proteins, Survivin, Borealin and INCENP. Each of the four components of the complex is required for the proper localization and function of the other three. INCENP stimulates Aurora B kinase activity. Survivin might do the same. Localization of Aurora B to the centromere during prometaphase and metaphase requires phosphorylation of the mammalian kinetochore-specific histone-H3 variant centromere protein A (CENP-A). CENP-A associates with the centromere and is necessary for assembly of the kinetochore. Phosphorylation of CENP-A at serine 7 by Aurora A kinase recruits Aurora B to the centromere. Aurora B, itself, can also phosphorylate CENP-A at the same residue once it is recruited (see below). Additionally, topoisomerase II has been implicated in the regulation of Aurora B localization and enzymatic activity. This regulatory role may be directly associated with the role of topoisomerase II in disjoining sister chromatids prior to anaphase. In topoisomerase II-depleted cells, Aurora B and INCENP do not transfer to the central spindle in late mitosis. Instead, they remain tightly associated with the centromeres of non-disjoined sister chromatids. Also, cells deficient in topoisomerase II show significantly reduced Aurora B kinase activity. Inhibition of Aurora B due to loss of topoisomerase II seems to depend on BubR1 activity (see below).