The tumour suppressor protein p53 can repress transcription of cyclin B

The tumour Suppressor protein p53 has functions in controlling the G(1)/S and G(2)/M transitions. Central regulators for progression from G(2) to mitosis are B-type cyclins complexed with cdc2 kinase, In mammals two cyclin B proteins are found, cyclin B1 and B2, We show that upon treatment of HepG2 cells with 5-fluorouracil or methotrexate, p53 levels increase while concentrations of cyclin B2 mRNA, measured by RT-PCR with the LightCycler system, are reduced, In DLD-1 colorectal adenocarcinoma cells (DLD-1-tet-off-p53) cyclin Bland,B2 mRNA levels drop after expression of wild-type p53 but not after induction of a DNA binding-deficient mutant of p53, Analysis of the cyclin: B2 promoter reveals specific repression of this gene by p53, Transfection of wild-type p53 into SaOS-2 Cells shuts off transcription from a cyclin B2 promoter-luciferase construct whereas a p53 mutant protein does not, The cyclin B2 promoter does not contain a consensus p53 binding site, Most of the p53-dependent transcriptional responsiveness resides in its 226 bp core promoter, Taken together with earlier:observations on p53-dependent transcription of cyclin BI, our results suggest that one way Of-regulating G(2) arrest may be a reduction in cyclin B levels through p53-dependent transcriptional repression.