The Xenopus laevis centrosome aurora/lpl1‐related kinase

Abstract

The cDNA encoding the protein kinase pEg2 was originally cloned through a differential screening performed during the early development of Xenopus laevis. pEg2 orthologues were found in various organisms and were classified in a new family of oncogenic mitotic protein kinases named 'aurora/Ipl1-related kinases' after the Drosophila melanogaster gene aurora and the Saccharomyces cerevisiae gene Ipl1. The catalytic activity of pEg2 is necessary for the mitotic microtubule spindle formation in Xenopus laevis egg extracts. The addition of a dominant negative form of pEg2 to in vitro spindle assembly assays leads to monopolar spindles generated by a defect of centrosome separation. In Xenopus cultured cells, pEg2 was confined around the pericentriolar material once centrosomes were duplicated. The centrosome localization does not depend on the presence of microtubules. However, in vitro, the protein binds to taxol-stabilized microtubules independently of its kinase activity. During mitosis the location of the protein changes, in metaphase the kinase localizes on the microtubules at the poles of the mitotic spindle whereas it is not present on astral microtubules. This localization persists until the segregation of the chromosomes is completed. The presence of the kinase on the spindle may reveal another yet unknown function.

On the role of aurora-A in centrosome function

“…A role of aurora-A in centrosome separation was confirmed in Xenopus egg extracts, in which inhibition of aurora-A during bipolar spindle formation by addition of an inactive recombinant protein kinase also leads to monopolar spindle (Roghi et al, 1998). Some of these monopolar spindles seemed to contain two centrosomes that failed to separate (Giet et al, 1999b). In contrast, during the first mitosis in C. elegans, aurora-A is not required for centrosome separation (Schumacher et al, 1998), although in the absence of the kinase bipolar mitotic spindles fail to assemble because centrosomes collapse together leading to monopolar spindle formation (Hannak et al, 2001).…”

Cep68 and Cep215 (Cdk5rap2) are required for centrosome cohesion

“…At the onset of mitosis, the activation of several protein kinases triggers centrosome separation, leading to the formation of a bipolar spindle (Berdnik and Knoblich, 2002;Blangy et al, 1995;Fry et al, 1998a;Giet et al, 1999;Glover et al, 1995;Hannak et al, 2001;Lane and Nigg, 1996;Sawin and Mitchison, 1995). However, before late G2 phase, the two centrosomes function as a single MTOC.…”

Suppression of p160ROCK bypasses cell cycle arrest after Aurora-A/STK15 depletion

“…Aurora-A is regulated by ubiquitin pathways and protein phosphorylation (16)(17)(18)(19). A kinesin-related protein (Eg5), cytoplasmic polyadenylation element-binding protein (CPEB), and transforming acidic coiled-coil protein number 3 (TACC3) have been found to be substrates of Aurora-A (20)(21)(22)(23).…”