Degradation of human Aurora-A protein kinase is mediated by hCdh1.
Human Aurora-A is related to a protein kinase originally identified by its close homology to Ipl1p from Saccharomyces cerevisiae and aurora from Drosophila melanogaster, which are key regulators of the structure and function of the mitotic spindle. We previously showed that human Aurora-A is turned over through the anaphase promoting complex/cyclosome (APC/C)-ubiquitin-proteasome pathway. The association of two distinct WD40 repeat proteins known as Cdc20 and Cdh1, respectively, sequentially activates the APC/C. The present study shows that Aurora-A degradation is dependent on hCdh1 in vivo, not on hCdc20, and that Aurora-A is targeted for proteolysis through distinct structural features of the destruction box, the KEN box motifs and its kinase activity.
Taguchi
Sei ichi
Si
Department of Biochemistry II, Nagoya University School of Medicine, 65 Tsurumai-machi, Showa-ku, Nagoya, Japan.
Honda
Kei
K
Sugiura
Kazumitsu
K
Yamaguchi
Akio
A
Furukawa
Koichi
K
Urano
Takeshi
T
D020816:Amino Acid Motifs / Q000502:physiology; D064173:Anaphase-Promoting Complex-Cyclosome; D000818:Animals; D064127:Aurora Kinases; D019556:COS Cells; D064199:Cdc20 Proteins; D002453:Cell Cycle / Q000502:physiology; D018797:Cell Cycle Proteins; D015870:Gene Expression / Q000502:physiology; D006367:HeLa Cells; D006801:Humans; D008025:Ligases / Q000235:genetics / Q000378:metabolism*; D046911:Macromolecular Substances; D011494:Protein Kinases / Q000235:genetics / Q000378:metabolism*; D017346:Protein Serine-Threonine Kinases; D011506:Proteins / Q000235:genetics / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D020449:Repetitive Sequences, Amino Acid / Q000502:physiology; D014162:Transfection; D043743:Ubiquitin-Protein Ligase Complexes; D029867:Xenopus Proteins
D064199:Cdc20 Proteins; D018797:Cell Cycle Proteins; D046911:Macromolecular Substances; D011506:Proteins; D011993:Recombinant Fusion Proteins; D029867:Xenopus Proteins; C577488:CDC20 protein, human; D043743:Ubiquitin-Protein Ligase Complexes; D064173:Anaphase-Promoting Complex-Cyclosome; D011494:Protein Kinases; C112134:AURKA protein, Xenopus; D064127:Aurora Kinases; D017346:Protein Serine-Threonine Kinases; D008025:Ligases