Plk1 regulates mitotic Aurora A function through betaTrCP-dependent degradation of hBora.
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Chan EH, Santamaria A, Sillje HH, Nigg EA
Plk1 regulates mitotic Aurora A function through betaTrCP-dependent degradation of hBora.
Chromosoma. 2008 Oct;117(5):457-69. doi: 10.1007/s00412-008-0165-5. Epub 2008 Jun 3.
- PubMed ID
- 18521620 [ View in PubMed]
- Abstract
Polo-like kinase 1 (Plk1) and Aurora A play key roles in centrosome maturation, spindle assembly, and chromosome segregation during cell division. Here we show that the functions of these kinases during early mitosis are coordinated through Bora, a partner of Aurora A first identified in Drosophila. Depletion of human Bora (hBora) results in spindle defects, accompanied by increased spindle recruitment of Aurora A and its partner TPX2. Conversely, hBora overexpression induces mislocalization of Aurora A and monopolar spindle formation, reminiscent of the phenotype seen in Plk1-depleted cells. Indeed, Plk1 regulates hBora. Following Cdk1-dependent recruitment, Plk1 triggers hBora destruction by phosphorylating a recognition site for SCF(Beta-TrCP). Plk1 depletion or inhibition results in a massive accumulation of hBora, concomitant with displacement of Aurora A from spindle poles and impaired centrosome maturation, but remarkably, co-depletion of hBora partially restores Aurora A localization and bipolar spindle formation. This suggests that Plk1 controls Aurora A localization and function by regulating cellular levels of hBora.