Physical interaction and mutual transrepression between CCAAT/enhancer-binding protein beta and the p53 tumor suppressor.
The tumor suppressor protein p53 is not only involved in defending cells against genotoxic insults but is also implicated in differentiation processes, a function that it shares with the CCAAT/enhancer-binding protein beta (C/EBPbeta). We previously reported an up-regulation of both factors in the cycle-dependent differentiation process of human endometrial stromal cells, termed decidualization. C/EBPbeta-mediated activation of a decidualization marker, the decidual prolactin promoter, was antagonized by p53. Here we report that C/EBPbeta in turn represses the transcriptional activity of p53. Competition for limiting amounts of coactivator CREB-binding protein/p300 was ruled out as the underlying mechanism of transrepression. Physical interaction between p53 and C/EBPbeta was demonstrated in vitro and in vivo and shown to depend on the C-terminal domains of both proteins. In gel shift experiments, C/EBPbeta reduced complex formation between p53 and its response element. Conversely, p53 strongly inhibited binding of endogenous C/EBPbeta from endometrial stromal cells to the C/EBP-responsive region in the decidual prolactin promoter. The observed negative cross-talk between p53 and C/EBPbeta is likely to impact expression of their respective target genes.
Schneider-Merck
Tanja
T
Endokrinologikum Hamburg, Falkenried, Hamburg 20251, Germany.
Pohnke
Yvonne
Y
Kempf
Rita
R
Christian
Mark
M
Brosens
Jan J
JJ
Gellersen
Birgit
B
D000818:Animals; D022782:CCAAT-Enhancer-Binding Protein-beta / Q000378:metabolism*; D019556:COS Cells; D045744:Cell Line, Tumor; D002522:Chlorocebus aethiops; D024202:Electrophoretic Mobility Shift Assay; D004717:Endometrium / Q000166:cytology; D005260:Female; D005786:Gene Expression Regulation / Q000502:physiology*; D006801:Humans; D012516:Osteosarcoma; D020218:Response Elements / Q000502:physiology; D017154:Stromal Cells / Q000166:cytology / Q000502:physiology*; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*; D050880:p300-CBP Transcription Factors / Q000378:metabolism
D022782:CCAAT-Enhancer-Binding Protein-beta; D016159:Tumor Suppressor Protein p53; D050880:p300-CBP Transcription Factors