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  • The EMBO Journal (2007) 26, 3968 - 3980
  • doi:10.1038/sj.emboj.7601825

Published online: 9 August 2007

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

Yi-Hung Ou1,ab, Pei-Han Chung1,ac, Fu-Fei Hsu1,2, Te-Ping Sun1,3, Wen-Ying Chang1 and Sheau-Yann Shieh1

  1. Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan
  2. Institute of Biochemistry and Molecular Biology, Molecular Medicine Program, National Yang-Ming University, Taipei, Taiwan
  3. Graduate Institute of Life Sciences, National Defense Medical Center, Taipei, Taiwan

Correspondence to:

Sheau-Yann Shieh, Institute of Biomedical Sciences, Academia Sinica, 128 Sec. 2, Academia Road, Taipei 115, Taiwan. Tel.: +886 2 26523916; Fax: +886 2 27829143; E-mail: sy88@ibms.sinica.edu.tw

aThese authors contributed equally to this work

bPresent address: Department of Cell Biology, University of Texas Southwestern Medical Center at Dallas, 5323 Harry Hines Blvd., Dallas, TX 75390, USA.

cPresent address: Institute of Molecular Biology, Academia Sinica, 128 Sec. 2, Academia Road, Taipei 115, Taiwan.

Received 27 February 2007; Accepted 17 July 2007

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 translocation gene 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.

  • Keywords:

    • BTG,
    • E2F1,
    • p53