Am J Cancer Res 2012;2(1):36-44
Original Article
The warts gene as a novel target of the Drosophila DRE/DREF transcription
pathway
Shunsuke Fujiwara, Hiroyuki Ida, Yasuhide Yoshioka, Hideki Yoshida, Masamitsu Yamaguchi
Department of Applied Biology, Insect Biomedical Research Center, Venture laboratory, Kyoto Institute of Technology
Matsugasaki, Sakyo-ku, Kyoto 606-8585, Japan.
Received September 15, 2011; accepted October 21, 2011; Epub November 22, 2011; Published January 1, 2012
Abstract: The Hippo tumor suppressor pathway in Drosophila represses expression of DIAP1 and Cyclin E via inactivation of the
transcription co-activator Yorkie, resulting in cell cycle arrest and induction of apoptosis. The warts (wts) gene is well known as a
core kinase in this pathway, but its transcriptional regulation has yet to be clarified. In Drosophila, DREF binds to a target
sequence named DRE (5’-TATCGATA) and regulates transcription of cell proliferation-related genes containing the DRE
sequence in their promoter regions. Here we found half reduction of the wts gene dose to enhance the DREF-induced rough eye
phenotype, suggesting a DREF genetic interaction with the Hippo pathway in vivo. Three DREs indentified in the wts gene
promoter region exhibited strong promoter activity with a luciferase transient expression assay in Drosophila S2 cells, this
decreasing under DREF-RNAi conditions. In addition, knockdown of DREF in S2 cells reduced the level of endogenous wts
mRNA. Chromatin immunoprecipitation assays with anti-DREF antibody revealed that DREF binds specifically to the wts gene
promoter region containing DREs in vivo. These results indicate that the DRE/DREF pathway is required for transcriptional
regulation of the wts gene, indicating a novel link between the DRE/DREF and the Hippo pathways. (AJCR0000087).
Keywords: DRE, DREF, warts, Hippo pathway, transcription, tumor suppressor
Full Text PDF
Address all correspondence to:
Dr. Masamitsu Yamaguchi
Department of Applied Biology, Insect Biomedical Research Center,
Kyoto Institute of Technology, Matsugasaki, Sakyo-ku
Kyoto 606-8585, Japan
E-mail: myamaguc@kit.ac.jp
Original Article
The warts gene as a novel target of the Drosophila DRE/DREF transcription
pathway
Shunsuke Fujiwara, Hiroyuki Ida, Yasuhide Yoshioka, Hideki Yoshida, Masamitsu Yamaguchi
Department of Applied Biology, Insect Biomedical Research Center, Venture laboratory, Kyoto Institute of Technology
Matsugasaki, Sakyo-ku, Kyoto 606-8585, Japan.
Received September 15, 2011; accepted October 21, 2011; Epub November 22, 2011; Published January 1, 2012
Abstract: The Hippo tumor suppressor pathway in Drosophila represses expression of DIAP1 and Cyclin E via inactivation of the
transcription co-activator Yorkie, resulting in cell cycle arrest and induction of apoptosis. The warts (wts) gene is well known as a
core kinase in this pathway, but its transcriptional regulation has yet to be clarified. In Drosophila, DREF binds to a target
sequence named DRE (5’-TATCGATA) and regulates transcription of cell proliferation-related genes containing the DRE
sequence in their promoter regions. Here we found half reduction of the wts gene dose to enhance the DREF-induced rough eye
phenotype, suggesting a DREF genetic interaction with the Hippo pathway in vivo. Three DREs indentified in the wts gene
promoter region exhibited strong promoter activity with a luciferase transient expression assay in Drosophila S2 cells, this
decreasing under DREF-RNAi conditions. In addition, knockdown of DREF in S2 cells reduced the level of endogenous wts
mRNA. Chromatin immunoprecipitation assays with anti-DREF antibody revealed that DREF binds specifically to the wts gene
promoter region containing DREs in vivo. These results indicate that the DRE/DREF pathway is required for transcriptional
regulation of the wts gene, indicating a novel link between the DRE/DREF and the Hippo pathways. (AJCR0000087).
Keywords: DRE, DREF, warts, Hippo pathway, transcription, tumor suppressor
Full Text PDF
Address all correspondence to:
Dr. Masamitsu Yamaguchi
Department of Applied Biology, Insect Biomedical Research Center,
Kyoto Institute of Technology, Matsugasaki, Sakyo-ku
Kyoto 606-8585, Japan
E-mail: myamaguc@kit.ac.jp
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American Journal of Cancer Research
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