title: Over-expression of Aurora-A targets cytoplasmic polyadenylation element binding protein and promotes mRNA polyadenylation of Cdk1 and cyclin B1.
abstract: Aurora-A is a centrosomal serine-threonine kinase that regulates mitosis. Over-expression of Aurora-A has been found in a wide range of tumors and has been implicated in oncogenic transformation. However, how Aurora-A over-expression contributes to promotion of carcinogenesis remains elusive. Immunohistochemical analysis of breast tumors revealed that over-expressed Aurora-A is not restricted to the centrosomes but is also found in the cytoplasm. This over-expressed Aurora-A appeared to be phosphorylated on Thr288, which is known to be required for its enzymatic activation. In analogy to Aurora-A's role in oocyte maturation and the early embryonic cell cycle, here we investigated whether ectopically over-expressed Aurora-A can similarly stimulate polyadenylation of mRNA in human somatic cultured cells by interacting with a human ortholog of cytoplasmic polyadenylation element binding protein, h-CPEB. In vitro experiments revealed that Aurora-A binds directly to, and phosphorylates, h-CPEB. We found that polyadenylation of mRNA tails of cyclin B1 and Cdk1 was synergistically stimulated when Aurora-A and h-CPEB were over-expressed, and they were further promoted in the presence of an Aurora-A activator Ajuba. Our results suggest a function of ectopically over-expressed Aurora-A that might be relevant for carcinogenesis.
authors.affiliation: Department of Tumor Genetics and Biology, Graduate School of Medical Sciences, Kumamoto University, 1-1-1 Honjo, Kumamoto 860-8556, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Sasayama
authors.forename: Tomotoshi
authors.initials: T
authors.lastname: Marumoto
authors.forename: Naoko
authors.initials: N
authors.lastname: Kunitoku
authors.forename: Dongwei
authors.initials: D
authors.lastname: Zhang
authors.forename: Norihiko
authors.initials: N
authors.lastname: Tamaki
authors.forename: Eiji
authors.initials: E
authors.lastname: Kohmura
authors.forename: Hideyuki
authors.initials: H
authors.lastname: Saya
authors.forename: Toru
authors.initials: T
authors.lastname: Hirota
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D064096:Aurora Kinase A; D064127:Aurora Kinases; D016203:CDC2 Protein Kinase / Q000235:genetics / Q000378:metabolism*; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism*; D002478:Cells, Cultured; D019926:Cyclin B / Q000235:genetics / Q000378:metabolism*; D056744:Cyclin B1; D018398:Homeodomain Proteins / Q000378:metabolism; D006801:Humans; D060588:LIM Domain Proteins; D008969:Molecular Sequence Data; D010766:Phosphorylation; D026723:Polyadenylation; D011494:Protein Kinases / Q000235:genetics / Q000378:metabolism*; D017346:Protein Serine-Threonine Kinases; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism*; D051381:Rats; D014157:Transcription Factors / Q000378:metabolism*; D029867:Xenopus Proteins / Q000235:genetics / Q000378:metabolism*; D039221:mRNA Cleavage and Polyadenylation Factors / Q000378:metabolism*
chemical_list: C119385:Ajuba protein, rat; C534699:CCNB1 protein, human; C490386:CPEB1 protein, human; C534701:Ccnb1 protein, rat; D018797:Cell Cycle Proteins; D019926:Cyclin B; D056744:Cyclin B1; D018398:Homeodomain Proteins; D060588:LIM Domain Proteins; D012333:RNA, Messenger; D014157:Transcription Factors; D029867:Xenopus Proteins; D039221:mRNA Cleavage and Polyadenylation Factors; D011494:Protein Kinases; C112134:AURKA protein, Xenopus; C576920:Aurka protein, rat; D064096:Aurora Kinase A; D064127:Aurora Kinases; D017346:Protein Serine-Threonine Kinases; D016203:CDC2 Protein Kinase