Thymine DNA glycosylase promotes transactivation of β-catenin/TCFs by cooperating with CBP.
Thymine DNA glycosylase (TDG), an enzyme that initiates the repair of G/T and G/U mismatches, has been lately found crucial in embryonic development to maintain epigenetic stability and facilitate the active DNA demethylation. Here we report a novel role of TDG in Wnt signaling as a transcriptional coactivator of β-catenin/TCFs ... complex. Our data show that TDG binds to the transcriptional factor family LEF1/TCFs and potentiates β-catenin/TCFs transactivation, while TDG depletion suppresses Wnt3a-stimulated reporter activity or target gene transcription. Next, we show that CBP, a known coactivator, is also required for TDG function through forming a cooperative complex on target promoters. Moreover, there is an elevation of TDG levels in human colon cancer tissue, and knockdown of TDG inhibits proliferation of the colon cells. Overall, our results reveal that TDG, as a new coactivator, promotes β-catenin/TCFs transactivation and functionally cooperates with CBP in canonical Wnt signaling.
Mesh Terms:
Animals, Colonic Neoplasms, HEK293 Cells, HeLa Cells, Humans, Lymphoid Enhancer-Binding Factor 1, Mice, Inbred C57BL, Peptide Fragments, Promoter Regions, Genetic, Protein Binding, Sialoglycoproteins, Thymine DNA Glycosylase, Transcriptional Activation, Up-Regulation, Wnt Signaling Pathway, beta Catenin
Animals, Colonic Neoplasms, HEK293 Cells, HeLa Cells, Humans, Lymphoid Enhancer-Binding Factor 1, Mice, Inbred C57BL, Peptide Fragments, Promoter Regions, Genetic, Protein Binding, Sialoglycoproteins, Thymine DNA Glycosylase, Transcriptional Activation, Up-Regulation, Wnt Signaling Pathway, beta Catenin
J Mol Cell Biol
Date: Jun. 01, 2014
PubMed ID: 24748645
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