Polo-like kinase-1 controls Aurora A destruction by activating APC/C-Cdh1.
Polo-like kinase-1 (Plk1) is activated before mitosis by Aurora A and its cofactor Bora. In mitosis, Bora is degraded in a manner dependent on Plk1 kinase activity and the E3 ubiquitin ligase SCF-betaTrCP. Here, we show that Plk1 is also required for the timely destruction of its activator Aurora A in late anaphase. It has been shown that Aurora A destruction is controlled by the auxiliary subunit Cdh1 of the Anaphase-Promoting Complex/Cyclosome (APC/C). Remarkably, we found that Plk1-depletion prevented the efficient dephosphorylation of Cdh1 during mitotic exit. Plk1 mediated its effect on Cdh1, at least in part, through direct phosphorylation of the human phosphatase Cdc14A, controlling the phosphorylation state of Cdh1. We conclude that Plk1 facilitates efficient Aurora A degradation through APC/C-Cdh1 activation after mitosis, with a potential role for hCdc14A.
van Leuken
Renske
R
Department of Medical Oncology, University Medical Centre Utrecht, Utrecht, The Netherlands.
Clijsters
Linda
L
van Zon
Wouter
W
Lim
Dan
D
Yao
XueBiao
X
Wolthuis
Rob M F
RM
Yaffe
Michael B
MB
Medema
René H
RH
van Vugt
Marcel A T M
MA
D000705:Anaphase; D064173:Anaphase-Promoting Complex-Cyclosome; D064127:Aurora Kinases; D015820:Cadherins / Q000378:metabolism*; D018797:Cell Cycle Proteins / Q000378:metabolism*; D045744:Cell Line, Tumor; D005434:Flow Cytometry; D006801:Humans; D008938:Mitosis; D010744:Phosphoric Monoester Hydrolases / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D043743:Ubiquitin-Protein Ligase Complexes / Q000378:metabolism*; D000097869:Polo-Like Kinase 1
D064173:Anaphase-Promoting Complex-Cyclosome; D064127:Aurora Kinases; D015820:Cadherins; D018797:Cell Cycle Proteins; D010744:Phosphoric Monoester Hydrolases; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins; D043743:Ubiquitin-Protein Ligase Complexes; D000097869:Polo-Like Kinase 1