DNA damage signalling recruits RREB-1 to the p53 tumour suppressor promoter.
Transcriptional regulation of the p53 tumour suppressor gene plays an important role in the control of the expression of various target genes involved in the DNA damage response. However, the molecular basis of this regulation remains obscure. In the present study we demonstrate that RREB-1 (Ras-responsive-element-binding protein-1) efficiently binds to the p53 promoter via the p53 core promoter element and transactivates p53 expression. Silencing of RREB-1 significantly reduces p53 expression at both the mRNA and the protein levels. Notably, disruption of RREB-1-mediated p53 transcription suppresses the expression of the p53 target genes. We also show that, upon exposure to genotoxic stress, RREB-1 controls apoptosis in a p53-dependent manner. These findings provide evidence that RREB-1 participates in modulating p53 transcription in response to DNA damage.
Liu
Hanshao
H
Department of Molecular Genetics, Medical Research Institute, Tokyo Medical and Dental University, Tokyo 113-8510, Japan.
Hew
Hoi Chin
HC
Lu
Zheng-Guang
ZG
Yamaguchi
Tomoko
T
Miki
Yoshio
Y
Yoshida
Kiyotsugu
K
D017209:Apoptosis / Q000235:genetics / Q000502:physiology; D001973:Bromodeoxyuridine / Q000378:metabolism; D002453:Cell Cycle / Q000235:genetics / Q000502:physiology; D045744:Cell Line, Tumor; D047369:Chromatin Immunoprecipitation; D004249:DNA Damage / Q000502:physiology* / Q000528:radiation effects; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D015151:Immunoblotting; D020287:In Situ Nick-End Labeling; D011401:Promoter Regions, Genetic / Q000235:genetics*; D011485:Protein Binding; D012333:RNA, Messenger / Q000235:genetics; D034741:RNA, Small Interfering; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism*; D014466:Ultraviolet Rays / Q000009:adverse effects
D004268:DNA-Binding Proteins; D012333:RNA, Messenger; D034741:RNA, Small Interfering; C101743:RREB1 protein, human; D014157:Transcription Factors; D016159:Tumor Suppressor Protein p53; D001973:Bromodeoxyuridine