The Aurora-A kinase has well-established roles in spindle assembly and function and is frequently overexpressed in tumours. Its abundance is cell cycle regulated, with a peak in G2 and M phases, followed by regulated proteolysis at the end of mitosis. The microtubule-binding protein TPX2 plays a major role in regulating the activity and localisation of Aurora-A in mitotic cells. Here, we report a novel regulatory role of TPX2 and show that it protects Aurora-A from degradation both in interphase and in mitosis in human cells. Specifically, Aurora-A levels decrease in G2 and prometaphase cells silenced for TPX2, whereas degradation of Aurora-A is impaired in telophase cells overexpressing the Aurora-A-binding region of TPX2. The decrease in Aurora-A in TPX2-silenced prometaphases requires proteasome activity and the Cdh1 activator of the APC/C ubiquitin ligase. Reintroducing either full-length TPX2, or the Aurora-A-binding region of TPX2, but not a truncated TPX2 mutant lacking the Aurora-A-interaction domain, restores Aurora-A levels in TPX2-silenced prometaphases. The control by TPX2 of Aurora-A stability is independent of its ability to activate Aurora-A and to localise it to the spindle. These results highlight a novel regulatory level impinging on Aurora-A and provide further evidence for the central role of TPX2 in regulation of Aurora-A.
机构:
Hiroshima Univ, Grad Sch Biomed Sci, Div Cervicognathostomatol, Dept Oral & Maxillofacial Surg,Minami Ku, Hiroshima 7348553, JapanHiroshima Univ, Grad Sch Biomed Sci, Div Cervicognathostomatol, Dept Oral & Maxillofacial Surg,Minami Ku, Hiroshima 7348553, Japan
Shigeishi, Hideo
Ohta, Kouji
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Hiroshima Univ, Grad Sch Biomed Sci, Div Cervicognathostomatol, Dept Oral & Maxillofacial Surg,Minami Ku, Hiroshima 7348553, JapanHiroshima Univ, Grad Sch Biomed Sci, Div Cervicognathostomatol, Dept Oral & Maxillofacial Surg,Minami Ku, Hiroshima 7348553, Japan
Ohta, Kouji
Hiraoka, Misato
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Hiroshima Univ, Grad Sch Biomed Sci, Div Cervicognathostomatol, Dept Oral & Maxillofacial Surg,Minami Ku, Hiroshima 7348553, JapanHiroshima Univ, Grad Sch Biomed Sci, Div Cervicognathostomatol, Dept Oral & Maxillofacial Surg,Minami Ku, Hiroshima 7348553, Japan
Hiraoka, Misato
Fujimoto, Shinichi
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h-index: 0
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Hiroshima Univ, Grad Sch Biomed Sci, Div Cervicognathostomatol, Dept Oral & Maxillofacial Surg,Minami Ku, Hiroshima 7348553, JapanHiroshima Univ, Grad Sch Biomed Sci, Div Cervicognathostomatol, Dept Oral & Maxillofacial Surg,Minami Ku, Hiroshima 7348553, Japan
Fujimoto, Shinichi
Minami, Masahiko
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h-index: 0
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Hiroshima Univ, Grad Sch Biomed Sci, Div Cervicognathostomatol, Dept Oral & Maxillofacial Surg,Minami Ku, Hiroshima 7348553, JapanHiroshima Univ, Grad Sch Biomed Sci, Div Cervicognathostomatol, Dept Oral & Maxillofacial Surg,Minami Ku, Hiroshima 7348553, Japan
Minami, Masahiko
Higashikawa, Koichiro
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Hiroshima Univ, Grad Sch Biomed Sci, Div Cervicognathostomatol, Dept Oral & Maxillofacial Surg,Minami Ku, Hiroshima 7348553, JapanHiroshima Univ, Grad Sch Biomed Sci, Div Cervicognathostomatol, Dept Oral & Maxillofacial Surg,Minami Ku, Hiroshima 7348553, Japan
Higashikawa, Koichiro
Kamata, Nobuyuki
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Hiroshima Univ, Grad Sch Biomed Sci, Div Cervicognathostomatol, Dept Oral & Maxillofacial Surg,Minami Ku, Hiroshima 7348553, JapanHiroshima Univ, Grad Sch Biomed Sci, Div Cervicognathostomatol, Dept Oral & Maxillofacial Surg,Minami Ku, Hiroshima 7348553, Japan
机构:
Univ British Columbia, Dept Pediat, Child & Family Res Inst, Vancouver, BC V6T 1W5, CanadaUniv British Columbia, Dept Pediat, Child & Family Res Inst, Vancouver, BC V6T 1W5, Canada
Chen, Helen
Mohan, Pooja
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h-index: 0
机构:
Univ British Columbia, Dept Pediat, Child & Family Res Inst, Vancouver, BC V6T 1W5, CanadaUniv British Columbia, Dept Pediat, Child & Family Res Inst, Vancouver, BC V6T 1W5, Canada
Mohan, Pooja
Jiang, Jihong
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h-index: 0
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Univ British Columbia, Dept Pediat, Child & Family Res Inst, Vancouver, BC V6T 1W5, CanadaUniv British Columbia, Dept Pediat, Child & Family Res Inst, Vancouver, BC V6T 1W5, Canada
Jiang, Jihong
Nemirovsky, Oksana
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Univ British Columbia, Dept Pediat, Child & Family Res Inst, Vancouver, BC V6T 1W5, CanadaUniv British Columbia, Dept Pediat, Child & Family Res Inst, Vancouver, BC V6T 1W5, Canada
Nemirovsky, Oksana
He, Daniel
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Univ British Columbia, Dept Pediat, Child & Family Res Inst, Vancouver, BC V6T 1W5, CanadaUniv British Columbia, Dept Pediat, Child & Family Res Inst, Vancouver, BC V6T 1W5, Canada
He, Daniel
Fleisch, Markus C.
论文数: 0引用数: 0
h-index: 0
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Univ Dusseldorf, Dept Gynaecol & Obstet, Univ Hosp Dusseldorf, Dusseldorf, GermanyUniv British Columbia, Dept Pediat, Child & Family Res Inst, Vancouver, BC V6T 1W5, Canada
Fleisch, Markus C.
Niederacher, Dieter
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h-index: 0
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Univ Dusseldorf, Dept Gynaecol & Obstet, Univ Hosp Dusseldorf, Dusseldorf, GermanyUniv British Columbia, Dept Pediat, Child & Family Res Inst, Vancouver, BC V6T 1W5, Canada
Niederacher, Dieter
Pilarski, Linda M.
论文数: 0引用数: 0
h-index: 0
机构:
Univ Alberta, Dept Oncol, Edmonton, AB, Canada
Cross Canc Inst, Edmonton, AB T6G 1Z2, CanadaUniv British Columbia, Dept Pediat, Child & Family Res Inst, Vancouver, BC V6T 1W5, Canada
Pilarski, Linda M.
Lim, C. James
论文数: 0引用数: 0
h-index: 0
机构:
Univ British Columbia, Dept Pediat, Child & Family Res Inst, Vancouver, BC V6T 1W5, CanadaUniv British Columbia, Dept Pediat, Child & Family Res Inst, Vancouver, BC V6T 1W5, Canada
Lim, C. James
Maxwell, Christopher A.
论文数: 0引用数: 0
h-index: 0
机构:
Univ British Columbia, Dept Pediat, Child & Family Res Inst, Vancouver, BC V6T 1W5, CanadaUniv British Columbia, Dept Pediat, Child & Family Res Inst, Vancouver, BC V6T 1W5, Canada
机构:
Hiroshima Univ, Grad Sch Biomed Sci, Div Cervicognathostomatol, Dept Oral & Maxillofacial Surg,Minami Ku, Hiroshima 7348553, JapanHiroshima Univ, Grad Sch Biomed Sci, Div Cervicognathostomatol, Dept Oral & Maxillofacial Surg,Minami Ku, Hiroshima 7348553, Japan
Shigeishi, Hideo
Ohta, Kouji
论文数: 0引用数: 0
h-index: 0
机构:
Hiroshima Univ, Grad Sch Biomed Sci, Div Cervicognathostomatol, Dept Oral & Maxillofacial Surg,Minami Ku, Hiroshima 7348553, JapanHiroshima Univ, Grad Sch Biomed Sci, Div Cervicognathostomatol, Dept Oral & Maxillofacial Surg,Minami Ku, Hiroshima 7348553, Japan
Ohta, Kouji
Hiraoka, Misato
论文数: 0引用数: 0
h-index: 0
机构:
Hiroshima Univ, Grad Sch Biomed Sci, Div Cervicognathostomatol, Dept Oral & Maxillofacial Surg,Minami Ku, Hiroshima 7348553, JapanHiroshima Univ, Grad Sch Biomed Sci, Div Cervicognathostomatol, Dept Oral & Maxillofacial Surg,Minami Ku, Hiroshima 7348553, Japan
Hiraoka, Misato
Fujimoto, Shinichi
论文数: 0引用数: 0
h-index: 0
机构:
Hiroshima Univ, Grad Sch Biomed Sci, Div Cervicognathostomatol, Dept Oral & Maxillofacial Surg,Minami Ku, Hiroshima 7348553, JapanHiroshima Univ, Grad Sch Biomed Sci, Div Cervicognathostomatol, Dept Oral & Maxillofacial Surg,Minami Ku, Hiroshima 7348553, Japan
Fujimoto, Shinichi
Minami, Masahiko
论文数: 0引用数: 0
h-index: 0
机构:
Hiroshima Univ, Grad Sch Biomed Sci, Div Cervicognathostomatol, Dept Oral & Maxillofacial Surg,Minami Ku, Hiroshima 7348553, JapanHiroshima Univ, Grad Sch Biomed Sci, Div Cervicognathostomatol, Dept Oral & Maxillofacial Surg,Minami Ku, Hiroshima 7348553, Japan
Minami, Masahiko
Higashikawa, Koichiro
论文数: 0引用数: 0
h-index: 0
机构:
Hiroshima Univ, Grad Sch Biomed Sci, Div Cervicognathostomatol, Dept Oral & Maxillofacial Surg,Minami Ku, Hiroshima 7348553, JapanHiroshima Univ, Grad Sch Biomed Sci, Div Cervicognathostomatol, Dept Oral & Maxillofacial Surg,Minami Ku, Hiroshima 7348553, Japan
Higashikawa, Koichiro
Kamata, Nobuyuki
论文数: 0引用数: 0
h-index: 0
机构:
Hiroshima Univ, Grad Sch Biomed Sci, Div Cervicognathostomatol, Dept Oral & Maxillofacial Surg,Minami Ku, Hiroshima 7348553, JapanHiroshima Univ, Grad Sch Biomed Sci, Div Cervicognathostomatol, Dept Oral & Maxillofacial Surg,Minami Ku, Hiroshima 7348553, Japan
机构:
Univ British Columbia, Dept Pediat, Child & Family Res Inst, Vancouver, BC V6T 1W5, CanadaUniv British Columbia, Dept Pediat, Child & Family Res Inst, Vancouver, BC V6T 1W5, Canada
Chen, Helen
Mohan, Pooja
论文数: 0引用数: 0
h-index: 0
机构:
Univ British Columbia, Dept Pediat, Child & Family Res Inst, Vancouver, BC V6T 1W5, CanadaUniv British Columbia, Dept Pediat, Child & Family Res Inst, Vancouver, BC V6T 1W5, Canada
Mohan, Pooja
Jiang, Jihong
论文数: 0引用数: 0
h-index: 0
机构:
Univ British Columbia, Dept Pediat, Child & Family Res Inst, Vancouver, BC V6T 1W5, CanadaUniv British Columbia, Dept Pediat, Child & Family Res Inst, Vancouver, BC V6T 1W5, Canada
Jiang, Jihong
Nemirovsky, Oksana
论文数: 0引用数: 0
h-index: 0
机构:
Univ British Columbia, Dept Pediat, Child & Family Res Inst, Vancouver, BC V6T 1W5, CanadaUniv British Columbia, Dept Pediat, Child & Family Res Inst, Vancouver, BC V6T 1W5, Canada
Nemirovsky, Oksana
He, Daniel
论文数: 0引用数: 0
h-index: 0
机构:
Univ British Columbia, Dept Pediat, Child & Family Res Inst, Vancouver, BC V6T 1W5, CanadaUniv British Columbia, Dept Pediat, Child & Family Res Inst, Vancouver, BC V6T 1W5, Canada
He, Daniel
Fleisch, Markus C.
论文数: 0引用数: 0
h-index: 0
机构:
Univ Dusseldorf, Dept Gynaecol & Obstet, Univ Hosp Dusseldorf, Dusseldorf, GermanyUniv British Columbia, Dept Pediat, Child & Family Res Inst, Vancouver, BC V6T 1W5, Canada
Fleisch, Markus C.
Niederacher, Dieter
论文数: 0引用数: 0
h-index: 0
机构:
Univ Dusseldorf, Dept Gynaecol & Obstet, Univ Hosp Dusseldorf, Dusseldorf, GermanyUniv British Columbia, Dept Pediat, Child & Family Res Inst, Vancouver, BC V6T 1W5, Canada
Niederacher, Dieter
Pilarski, Linda M.
论文数: 0引用数: 0
h-index: 0
机构:
Univ Alberta, Dept Oncol, Edmonton, AB, Canada
Cross Canc Inst, Edmonton, AB T6G 1Z2, CanadaUniv British Columbia, Dept Pediat, Child & Family Res Inst, Vancouver, BC V6T 1W5, Canada
Pilarski, Linda M.
Lim, C. James
论文数: 0引用数: 0
h-index: 0
机构:
Univ British Columbia, Dept Pediat, Child & Family Res Inst, Vancouver, BC V6T 1W5, CanadaUniv British Columbia, Dept Pediat, Child & Family Res Inst, Vancouver, BC V6T 1W5, Canada
Lim, C. James
Maxwell, Christopher A.
论文数: 0引用数: 0
h-index: 0
机构:
Univ British Columbia, Dept Pediat, Child & Family Res Inst, Vancouver, BC V6T 1W5, CanadaUniv British Columbia, Dept Pediat, Child & Family Res Inst, Vancouver, BC V6T 1W5, Canada