Skip to main content

Advertisement

Fig. 3 | Cell Division

Fig. 3

From: The functional diversity of Aurora kinases: a comprehensive review

Fig. 3

Role of AurA and AurB in mitosis. The cell-cycle dependent transcription of AurA and AurB are under the control of the CDE/CHR elements, which are recognized by the E4TF1 transcription factor. AurA is mainly activated after Thr288 auto-phosphorylation. Bora, a key AurA co-factor, is phosphorylated by AurA and, in return, Bora enhances the kinase activity of AurA. Once activated, AurA phosphorylates and activates CDK1-Cyclin B to allow G2/M checkpoint unlock through various mechanisms, including: (i) PLK1-dependent targeting of Wee1 and CDC25C, (ii) CDC25B-dependent activation of CDK1 and (ii) direct phosphorylation of CDK1. Then, PLK1 mediates Bora degradation to permit mitosis progression. At G2/M, AurA localizes in the centrosome and also contributes to their maturation before mitotic entry. At prophase, AurA—whose activity is maintained by Ajuba- recruits and phosphorylates several PCM proteins (i.e. γ-TuRC, centrosomin, NDEL1, TACC, LATS2 and BRCA1) to organize the MTOC. At metaphase, AurA moves to the proximal MT and targets MT-associated proteins (i.e. Ki2a, TACC3, CKAP5-a) to organize the mitotic spindle. At this time, TPX2 allows the maintenance of the activate state of AurA. AurB binds INCENP, Survivin and Borealin to form the CPC complex and to be activated upon Thr232 auto-phosphorylation. AurB, firstly localized on chromosomes, contributes to their proper alignment at metaphase. Prior anaphase, AurB concentrates to the kinetochore to allow the spindle assembly checkpoint (SAC) crossing through (i) H2AX-dependent activation of SAC sensors and (ii) Kif2C recruitment. Then, AurB moves to the central MT to trigger sister chromatids separation through Centralspindlin and SGO1 recruitment at anaphase. Finally, AurB targets various cytoskeleton regulatory proteins (RhoA, Vimentin, Desmin, GFAP) at the midbody in order to organize the cleavage furrow for cytokinesis. At the end of mitosis, both AurA and AurB undergo ubiquitination and proteasome degradation by APC/C, which happen subsequently to their dephosphorylation by PP2A or PP1

Back to article page