The candidate tumor suppressor BTG3 is a transcriptional target of p53 that inhibits E2F1

• Published in: The EMBO journal Vol. 26; no. 17; pp. 3968 - 3980
• Main Authors: Ou, Yi-Hung, Chung, Pei-Han, Hsu, Fu-Fei, Sun, Te-Ping, Chang, Wen-Ying, Shieh, Sheau-Yann
• Format: Journal Article
• Language: English
• Published: Chichester, UK John Wiley & Sons, Ltd 05.09.2007; Nature Publishing Group UK; Springer Nature B.V; Nature Publishing Group
• Subjects: BTG; Cell cycle; Cell Line, Tumor; Cellular biology; Deoxyribonucleic acid; DNA; DNA Damage; E2F1; E2F1 Transcription Factor - antagonists & inhibitors; E2F1 Transcription Factor - metabolism; Genomics; Humans; Inhibitor drugs; Introns; Molecular biology; Oligonucleotide Array Sequence Analysis; p53; Protein Binding; Proteins - genetics; Proteins - metabolism; Transcriptional Activation; Translocation; Tumor Suppressor Protein p53 - genetics; Tumor Suppressor Protein p53 - metabolism; Tumors; BTG; E2F1; p53
• ISSN: 0261-4189; 1460-2075; 1460-2075
• DOI: 10.1038/sj.emboj.7601825

Proper regulation of cell cycle progression is pivotal for maintaining genome stability. In a search for DNA damage‐inducible, CHK1‐modulated genes, we have identified BTG3 ( B ‐cell t ranslocation g ene 3) as a direct p53 target. The p53 transcription factor binds to a consensus sequence located in intron 2 of the gene both in vitro and in vivo , and depletion of p53 by small interfering RNA (siRNA) abolishes DNA damage‐induced expression of the gene. Furthermore, ablation of BTG3 by siRNA in cancer cells results in accelerated exit from the DNA damage‐induced G2/M block. In vitro , BTG3 binds to and inhibits E2F1 through an N‐terminal domain including the conserved box A. Deletion of the interaction domain in BTG3 abrogates not only its growth suppression activity, but also its repression on E2F1‐mediated transactivation. We also present evidence that by disrupting the DNA binding activity of E2F1, BTG3 participates in the regulation of E2F1 target gene expression. Therefore, our studies have revealed a previously unidentified pathway through which the activity of E2F1 may be guarded by activated p53.