Cell-cycle-dependent regulation of the human and mouse Tome-1 promoters.

Tome-1, which refers to a trigger of mitotic entry 1, mediates the destruction of the mitosis-inhibitory kinase, Wee1, via the E3 ligase, SCF. In turn, Tome-1 itself is targeted for degradation by APC in the G1 phase of the cell cycle. In the present study, we analyzed the human and mouse Tome-1 promoter regions. Using synchronized cultures of NIH3T3 cells transfected with Tome-1 promoter/luciferase constructs, we showed that the promoter activity of Tome-1 is activated at the G2/M phase. Using various Tome-1 promoter/luciferase constructs, we showed that the CCAAT box located upstream of the transcription initiation site is important for the basal promoter activity. We identified a repressor element (cell-cycle-dependent element/cell cycle gene homology region) in the vicinity of the transcription start site, and mutations within this element diminished the cell-cycle-dependent transcriptional regulation of Tome-1.