title: Thymine DNA glycosylase promotes transactivation of β-catenin/TCFs by cooperating with CBP.
abstract: 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.
authors.affiliation: State Key Laboratory of Molecular Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China.
authors.forename: Yingying
authors.initials: Y
authors.lastname: Jia
authors.affiliation: State Key Laboratory of Molecular Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China.
authors.forename: Fen
authors.initials: F
authors.lastname: Nie
authors.affiliation: State Key Laboratory of Molecular Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China.
authors.forename: Aiying
authors.initials: A
authors.lastname: Du
authors.affiliation: State Key Laboratory of Molecular Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China.
authors.forename: Zhangcheng
authors.initials: Z
authors.lastname: Chen
authors.affiliation: State Key Laboratory of Molecular Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China.
authors.forename: Yuanbo
authors.initials: Y
authors.lastname: Qin
authors.affiliation: State Key Laboratory of Molecular Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China.
authors.forename: Tao
authors.initials: T
authors.lastname: Huang
authors.affiliation: State Key Laboratory of Molecular Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China.
authors.forename: Xiaomin
authors.initials: X
authors.lastname: Song
authors.affiliation: State Key Laboratory of Molecular Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China lli@sibs.ac.cn.
authors.forename: Lin
authors.initials: L
authors.lastname: Li
mesh_terms: D000818:Animals; D003110:Colonic Neoplasms / Q000378:metabolism / Q000473:pathology; D057809:HEK293 Cells; D006367:HeLa Cells; D006801:Humans; D051821:Lymphoid Enhancer-Binding Factor 1 / Q000235:genetics* / Q000378:metabolism; D008810:Mice, Inbred C57BL; D010446:Peptide Fragments / Q000378:metabolism*; D011401:Promoter Regions, Genetic / Q000235:genetics; D011485:Protein Binding / Q000235:genetics; D012795:Sialoglycoproteins / Q000378:metabolism*; D044502:Thymine DNA Glycosylase / Q000378:metabolism*; D015533:Transcriptional Activation / Q000235:genetics*; D015854:Up-Regulation / Q000235:genetics; D060449:Wnt Signaling Pathway / Q000235:genetics; D051176:beta Catenin / Q000235:genetics* / Q000378:metabolism
chemical_list: C497574:Lef1 protein, mouse; D051821:Lymphoid Enhancer-Binding Factor 1; D010446:Peptide Fragments; D012795:Sialoglycoproteins; D051176:beta Catenin; C571744:bone sialoprotein (35-62), human; D044502:Thymine DNA Glycosylase
keywords: CBP; TCF; TDG; Wnt signaling; transactivation