Trends in Cell Biology
ReviewThe Aurora/Ipl1p kinase family: regulators of chromosome segregation and cytokinesis
Section snippets
Yeast and invertebrate aurora-family kinases
The founding members of the aurora family of serine/threonine kinases are Ipl1p (for: ‘increases in ploidy 1’) and aurora from Saccharomyces cerevisiae and Drosophila melanogaster, respectively. Ipl1p was identified in a genetic screen for mutations that lead to increases in chromosome missegregation8. ipl1 mutants have apparently normal mitotic spindles but exhibit unequal intensities of DNA staining at the poles of the mitotic spindle, indicative of missegregation of chromosomes and
Protein structure and classification of the aurora kinases
Evolutionarily, the auroras first appear in the eukaryotic lineage with a single member found in both budding (Ipl1p) and fission (spcc330.16) yeast. As their primary role is in centrosome segregation and cytokinesis, it is not surprising that they are absent from prokaryotes. Among S. cerevisiae proteins, Ipl1p is distantly related (29–35% amino acid sequence identity) to members of the protein kinase A family and Cdc5p, a gene product required for exit from mitosis. The catalytic domain of
Mammalian aurora1 kinases
Human aurora1 was first isolated in a PCR screen to identify protein kinases that are overexpressed in colon carcinomas16, whereas rat aurora1 (AIM1: ‘Aurora and Ipl1-like midbody-associated protein 1’) was cloned in a screen to isolate novel protein kinases that perturb growth when overexpressed in S. cerevisiae17. The 1.4-kb aurora1 transcript is abundant in tissues with a high mitotic index such as thymus, primary epithelial cells and fetal liver and is expressed at low levels in other
Mammalian aurora2 kinases
Like aurora1, the first full-length human aurora2 clone was isolated in a PCR screen to identify protein kinases that are overexpressed in colon carcinomas16. A partial clone had been reported previously as BTAK (breast-tumour-amplified kinase) in a search for genes residing on the 20q13 amplicon prevalent in several human tumour types22. Additional human aurora2 clones were reported as ARK1 (Aurora-related kinase 1)18 and AIK (Aurora/IPL1-related kinase)21. Murine orthologues of aurora2
Aurora2 and cancer
Given the preponderance of chromosomal abnormalities found in human cancer, it is appealing to propose that genes involved in chromosome segregation such as aurora2 contribute to this phenotype. The overexpression of human aurora2 in colorectal carcinomas and mapping of the aurora2 gene to human chromosome 20q1316, 22, 26 were the first clues that aurora2 might be involved in cancer. Amplification at 20q13 is common to a variety of human malignancies especially from colon, stomach and breast31,
Conclusions and speculations
It is clear that the Aurora/Ipl1p family of protein kinases are important regulators of mitosis (Fig. 4). Aurora1 kinases are required for cytokinesis, and their loss leads to aneuploidy. Aurora2 kinases function earlier in mitosis than aurora1 and might be involved in the assembly of the mitotic spindle as well as in microtubule–kinetochore interactions. Contrary to what is found in aurora mutants in Drosophila12, loss of aurora2 in other organisms does not cause a defect in centrosome
Acknowledgements
We thank Sara Courtneidge for her editorial comments and encouragement. We sincerely apologize to any authors whose work we failed to cite.
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