Increased levels of expression of the genes AURKA and WDR62 are observed in many cancers, including glioma. Both genes encode cell cycle-regulated proteins required for progression through mitosis. The orthologous Drosophila genes are aurA and Wdr62; loss-of-function mutations, RNAi-targeting constructs, and alleles caused by insertional mutagenesis have been generated for both fly genes. There are additional paralogous genes in human in both cases; in the case of AURKA there is a second orthologous gene, aurB, in flies.
Neither human gene, AURKA nor WDR62, has been introduced into flies.
Elevated levels of Wdr62 in glia significantly increases brain volume, glial number, and the percentage of glia in mitosis; a cell non-autonomous increase in neuroblast number and mitotic index is also observed. Overexpression of Wdr62 in neuroblasts also increases the number of NBs and is associated with a corresponding increase in brain size, but the phenotype is less profound than is observed for glial-specific overexpression.
Analysis of double mutants indicates that increased Wdr62 expression drives glial proliferation and brain overgrowth in a manner dependent on aurA.
See also the human disease reports ‘microcephaly 2, primary, autosomal recessive’ (FBhh0000329), a disease caused by loss of function variants of WDR62; and ‘cancer, neural stem cell, centrosome dysfunction’ (FBhh0000780), in which aurA and other genes that affect centrosome function have been assessed for capacity to produce tumors in a larval brain system.
[updated Sep. 2020 by FlyBase; FBrf0222196]
AURKA encodes a cell cycle-regulated kinase that appears to be involved in microtubule formation and/or stabilization at the spindle pole during chromosome segregation. The encoded protein is found at the centrosome in interphase cells and at the spindle poles in mitosis. [Gene Cards, AURKA; 2020.09.10]
WDR62 is a mitotic phosphoprotein localized to spindle poles from prophase to metaphase in a process that requires microtubule-dependent transport. In a study using human neural cells in culture, WDR62 was found to be required for proper progression through mitosis (Bogoyevitch et al., 2012; pubmed:22899712).
AURKA phosphorylation of WDR62 recruits the latter to bipolar spindle poles at mitotic entry (FBrf0245775 and references cited therein).
Many to many: 3 human to 2 Drosophila.
Many to one: 2 human to 1 Drosophila; additional orthologous human gene is MAPKBP1.
High-scoring ortholog of human AURKB, AURKC, and AURKA (2 Drosophila to 3 human). Dmel\aurA shares 48-55% identity and 64-74% similarity with the human genes.
High-scoring ortholog of human genes WDR62 and MAPKBP1 (1 Drosophila to 2 human). Dmel\Wdr62 shares 33-34% identity and 46-49% similarity with the human genes.
