Abstract
BackgroundThe AURKB gene encodes aurora kinase B (AURKB), which acts as a key regulator of mitosis. Aurora kinase B is overexpressed in many cancers at both the protein and mRNA levels; overexpression is associated with metastasis. This study aimed to find novel regulators of AURKB transcription. MethodsA bioinformatic approach was used to identify consensus factor binding sites in the AURKB promoter. An AURKB promoter-luciferase construct was generated containing the human AURKB promoter. Cotransfection of this construct with expression plasmids and analysis of transactivation was used to determine whether overexpression of factors identified by conservation and motif analysis had any functional effect on AURKB promoter activity in human 293T cells. Chromatin immunoprecipitation using chromatin from mouse resting B cells and electromobility shift assays using extracts from A549 cells, a human lung cancer cell line, were used to confirm DNA binding FindingsThe AURKB promoter contained a consensus-binding site for early growth response protein 1 (EGR1). Chromatin immunoprecipitation showed that EGR1 binds to the AURKB promoter in mouse resting B cells. The electromobility shift assay demostrated binding of EGR1 to the consensus binding site in the human AURKB promoter. The identity of the bound protein was confirmed by antibody supershift. Transactivation assays showed an increase in AURKB promoter activity when EGR1 was overexpressed. InterpretationEGR1 might be involved in regulating the expression of AURKB. Abnormal AURKB activity results in disruption of the normally tightly regulated process of cell division, and inhibitors of AURKB are being tested in clinical trials. Therefore an understanding of the regulation of AURKB and identification of factors that might affect its dysregulation in cancer could expedite the therapeutic potential of targeting aurora kinase B. FundingMedical Research Council, National Institute for Health Research Imperial Biomedical Research Centre.
Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
