The tumour suppressor protein p53 can repress transcription of cyclin B
AUTOR(ES)
Krause, Karen
FONTE
Oxford University Press
RESUMO
The tumour suppressor protein p53 has functions in controlling the G1/S and G2/M transitions. Central regulators for progression from G2 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 B1 and 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 B1, our results suggest that one way of regulating G2 arrest may be a reduction in cyclin B levels through p53-dependent transcriptional repression.
ACESSO AO ARTIGO
http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=113869Documentos Relacionados
- Cyclin G is a transcriptional target of the p53 tumor suppressor protein.
- The DEAD box protein p68: a novel transcriptional coactivator of the p53 tumour suppressor
- NEW EMBO MEMBER’S REVIEW: Hsp70 interactions with the p53 tumour suppressor protein
- The p53 tumour suppressor inhibits glucocorticoid-induced proliferation of erythroid progenitors
- The p53 tumour suppressor protein is phosphorylated at serine 389 by casein kinase II.