title: Degradation of human Aurora-A protein kinase is mediated by hCdh1.
abstract: 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.
authors.affiliation: Department of Biochemistry II, Nagoya University School of Medicine, 65 Tsurumai-machi, Showa-ku, Nagoya, Japan.
authors.forename: Sei ichi
authors.initials: Si
authors.lastname: Taguchi
authors.forename: Kei
authors.initials: K
authors.lastname: Honda
authors.forename: Kazumitsu
authors.initials: K
authors.lastname: Sugiura
authors.forename: Akio
authors.initials: A
authors.lastname: Yamaguchi
authors.forename: Koichi
authors.initials: K
authors.lastname: Furukawa
authors.forename: Takeshi
authors.initials: T
authors.lastname: Urano
mesh_terms: 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
chemical_list: 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