Plk1 regulates mitotic Aurora A function through betaTrCP-dependent degradation of hBora.
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.
Chan
Eunice H Y
EH
Department of Cell Biology, Max Planck Institute of Biochemistry, 82152 Martinsried, Germany.
Santamaria
Anna
A
Silljé
Herman H W
HH
Nigg
Erich A
EA
D000595:Amino Acid Sequence; D000818:Animals; D064096:Aurora Kinase A; D064127:Aurora Kinases; D018797:Cell Cycle Proteins / Q000187:drug effects / Q000378:metabolism*; D018385:Centrosome / Q000502:physiology; D020868:Gene Silencing; D006367:HeLa Cells; D006801:Humans; D051379:Mice; D008938:Mitosis / Q000502:physiology; D008969:Molecular Sequence Data; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000235:genetics; D044843:SKP Cullin F-Box Protein Ligases / Q000378:metabolism; D008941:Spindle Apparatus / Q000502:physiology; D044844:beta-Transducin Repeat-Containing Proteins / Q000235:genetics / Q000378:metabolism*; D000097869:Polo-Like Kinase 1
D064096:Aurora Kinase A; D064127:Aurora Kinases; D018797:Cell Cycle Proteins; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins; D034741:RNA, Small Interfering; D044843:SKP Cullin F-Box Protein Ligases; D044844:beta-Transducin Repeat-Containing Proteins; D000097869:Polo-Like Kinase 1; C528235:bora protein, human; C576918:Aurka protein, mouse