title: Identification of Aurora-A as a direct target of E2F3 during G2/M cell cycle progression.
abstract: Aurora-A is a centrosome kinase and plays a pivotal role in G(2)/M cell cycle progression. Expression of Aurora-A is cell cycle-dependent. Levels of Aurora-A mRNA and protein are low in G(1)/S, accumulate during G(2)/M, and decrease rapidly after mitosis. Previous studies have shown regulation of the Aurora-A protein level during the cell cycle through the ubiquitin-proteasome pathway. However, the mechanism of transcriptional regulation of Aurora-A remains largely unknown. Here, we demonstrated that E2F3 modulates Aurora-A mRNA expression during the cell cycle. Ectopic expression of E2F3 induces Aurora-A expression. Stable knockdown of E2F3 decreases mRNA and protein levels of Aurora-A and delays G(2)/M entry. Further, E2F3 directly binds to Aurora-A promoter and stimulates the promoter activity. Deletion and mutation analyses of the Aurora-A promoter revealed that a region located 96-bp upstream of the transcription initiation site is critical for the activation of the promoter by E2F3. In addition, expression of E2F3 positively correlates with the protein level of Aurora-A in human ovarian cancer examined. These results indicate for the first time that Aurora-A is transcriptionally regulated by E2F3 during the cell cycle and that E2F3 is a causal factor for up-regulation of Aurora-A in a subset of human ovarian cancer. Thus, the E2F3-Aurora-A axis could be an important target for cancer intervention.
authors.affiliation: Molecular Oncology Department, H. Lee Moffitt Cancer Center & Research Institute, Tampa, Florida 133612, USA.
authors.forename: Lili
authors.initials: L
authors.lastname: He
authors.forename: Hua
authors.initials: H
authors.lastname: Yang
authors.forename: Yihong
authors.initials: Y
authors.lastname: Ma
authors.forename: W Jack
authors.initials: WJ
authors.lastname: Pledger
authors.forename: W Douglas
authors.initials: WD
authors.lastname: Cress
authors.forename: Jin Q
authors.initials: JQ
authors.lastname: Cheng
mesh_terms: D000818:Animals; D064096:Aurora Kinase A; D064127:Aurora Kinases; D050699:E2F3 Transcription Factor / Q000235:genetics / Q000378:metabolism*; D005260:Female; D016195:G2 Phase / Q000235:genetics; D015971:Gene Expression Regulation, Enzymologic; D015972:Gene Expression Regulation, Neoplastic; D055785:Gene Knockdown Techniques; D006367:HeLa Cells; D006801:Humans; D008677:Metaphase; D051379:Mice; D041681:NIH 3T3 Cells; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism*; D010051:Ovarian Neoplasms / Q000235:genetics / Q000378:metabolism*; D017346:Protein Serine-Threonine Kinases / Q000096:biosynthesis* / Q000235:genetics; D020218:Response Elements / Q000235:genetics; D014158:Transcription, Genetic / Q000235:genetics; D015854:Up-Regulation / Q000235:genetics
chemical_list: D050699:E2F3 Transcription Factor; C098319:E2F3 protein, human; C490840:E2f3 protein, mouse; D009363:Neoplasm Proteins; C576918:Aurka protein, mouse; D064096:Aurora Kinase A; D064127:Aurora Kinases; D017346:Protein Serine-Threonine Kinases
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