E2F1 represses beta-catenin/TCF activity by  direct up-regulation of Siah1.
Transcription factor E2F1 is a key regulator of cell proliferation and apoptosis. Its activity is strictly controlled by the pRB/E2F pathway. In the majority of cancer cells, however, this pathway is frequently found deregulated, and the underlying mechanism involving transcriptional control by E2F1 has not yet been fully elucidated. Here we report the identification of two putative E2F1-binding sites located upstream from Siah1 transcription start site (+1). Chromatin immunoprecipitation assay reveals that transcription factor E2F1 is capable of binding to the putative sites, and luciferase reporter assay shows that E2F1 can activate transcription from the Siah1 promoter. Ectopic expression of E2F1 elevates the Siah1 level, hence suppressing the beta-catenin/TCF activity. Consistently, knock-down of endogenous E2F1 by a shRNA strategy results in reduced expression of Siah1. Moreover, repression of beta-catenin/TCF activity by E2F1 can be attenuated by shRNA-based repression of endogenous Siah1, implying that Siah1 is a bona fide E2F1 target gene, which at least partly, mediates the suppression of beta-catenin/TCF signalling pathway.
Xie
Wei
W
Hefei National Laboratory for Physical Sciences at Microscale and School of Life Sciences, University of Science and Technology of China, Hefei, Anhui, China.
Jin
Lei
L
Hefei National Laboratory for Physical Sciences at Microscale and School of Life Sciences, University of Science and Technology of China, Hefei, Anhui, China.
Mei
Yide
Y
Hefei National Laboratory for Physical Sciences at Microscale and School of Life Sciences, University of Science and Technology of China, Hefei, Anhui, China.
Wu
Mian
M
Hefei National Laboratory for Physical Sciences at Microscale and School of Life Sciences, University of Science and Technology of China, Hefei, Anhui, China.
D001483:Base Sequence; D045744:Cell Line, Tumor; D047369:Chromatin Immunoprecipitation; D017931:DNA Primers; D050687:E2F1 Transcription Factor / Q000502:physiology*; D006801:Humans; D009687:Nuclear Proteins / Q000378:metabolism*; D051820:TCF Transcription Factors / Q000378:metabolism*; D044767:Ubiquitin-Protein Ligases / Q000378:metabolism*; D015854:Up-Regulation / Q000502:physiology*; D051176:beta Catenin / Q000378:metabolism*; D000098563:Seven in Absentia Proteins
D017931:DNA Primers; D050687:E2F1 Transcription Factor; C493753:E2F1 protein, human; D009687:Nuclear Proteins; D051820:TCF Transcription Factors; D051176:beta Catenin; D044767:Ubiquitin-Protein Ligases; D000098563:Seven in Absentia Proteins