Degradation of human Aurora2 protein kinase by the anaphase-promoting complex-ubiquitin-proteasome pathway.
Human Aurora2 was originally identified by its close homology to yeast IPL1 and fly aurora, which are key regulators of chromosome segregation and a family of serine/threonine kinases. Here we demonstrate that the Aurora2 protein is degraded rapidly after G2/M phase release in mammalian cells. Aurora2 protein has a rapid turnover rate with a half-life of approximately 2 h. In eukaryotic cells, the ubiquitin-proteasome pathway is the major mechanism for the targeted degradation of unstable proteins. The treatment of mammalian cells with proteasome inhibitors blocks Aurora2 degradation. Furthermore, Aurora2 is polyubiquitinated in vivo and in vitro using anaphase-promoting complex (APC). These results demonstrate that Aurora2 protein is turned over through the APC-ubiquitin-proteasome pathway. Oncogene (2000) 19, 2812 - 2819
Honda
K
K
Department of Biochemistry II, Nagoya University School of Medicine, 65 Tsurumai-machi, Showa-ku, Nagoya 466-0065, Japan.
Mihara
H
H
Kato
Y
Y
Yamaguchi
A
A
Tanaka
H
H
Yasuda
H
H
Furukawa
K
K
Urano
T
T
D064173:Anaphase-Promoting Complex-Cyclosome; D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D064127:Aurora Kinases; D019556:COS Cells; D003546:Cysteine Endopeptidases / Q000502:physiology*; D006801:Humans; D008025:Ligases / Q000502:physiology*; D051379:Mice; D009097:Multienzyme Complexes / Q000502:physiology*; D046988:Proteasome Endopeptidase Complex; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D043743:Ubiquitin-Protein Ligase Complexes; D044767:Ubiquitin-Protein Ligases; D014452:Ubiquitins / Q000502:physiology*
D000911:Antibodies, Monoclonal; D009097:Multienzyme Complexes; D014452:Ubiquitins; D043743:Ubiquitin-Protein Ligase Complexes; D064173:Anaphase-Promoting Complex-Cyclosome; D044767:Ubiquitin-Protein Ligases; D064127:Aurora Kinases; D017346:Protein Serine-Threonine Kinases; D003546:Cysteine Endopeptidases; D046988:Proteasome Endopeptidase Complex; D008025:Ligases