Cell-cycle-dependent regulation of human aurora A transcription is mediated by periodic repression of E4TF1.
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Tanaka M, Ueda A, Kanamori H, Ideguchi H, Yang J, Kitajima S, Ishigatsubo Y
Cell-cycle-dependent regulation of human aurora A transcription is mediated by periodic repression of E4TF1.
J Biol Chem. 2002 Mar 22;277(12):10719-26. Epub 2002 Jan 14.
- PubMed ID
- 11790771 [ View in PubMed]
- Abstract
Human aurora A is a serine-threonine kinase that controls various mitotic events. The transcription of aurora A mRNA varies throughout the cell cycle and peaks during G(2)/M. To clarify the transcriptional mechanism, we first cloned the 1.8-kb 5'-flanking region of aurora A including the first exon. Transient expression of aurora A promoter-luciferase constructs containing a series of 5'-truncated sequences or site-directed mutations identified a 7-bp sequence (CTTCCGG) from -85 to -79 as a positive regulatory element. Electromobility shift assays identified the binding of positive regulatory proteins to the CTTCCGG element. Anti-E4TF1-60 antibody generated a supershifted complex. Furthermore, coexpression of E4TF1-60 and E4TF1-53 markedly increased aurora A promoter activity. Synchronized cells transfected with the aurora A promoter-luciferase constructs revealed that the promoter activity of aurora A increased in the S phase and peaked at G(2)/M. In addition, we identified a tandem repressor element, CDE/CHR, just downstream of the CTTCCGG element, and mutation within this element led to a loss of cell cycle regulation. We conclude that the transcription of aurora A is positively regulated by E4TF1, a ubiquitously expressed ETS family protein, and that the CDE/CHR element was essential for the G(2)/M-specific transcription of aurora A.