title: Enrichment of the β-catenin-TCF complex at the S and G2 phases ensures cell survival and cell cycle progression.
abstract: Wnt-β-catenin (β-catenin is also known as CTNNB1 in human) signaling through the β-catenin-TCF complex plays crucial roles in tissue homeostasis. Wnt-stimulated β-catenin-TCF complex accumulation in the nucleus regulates cell survival, proliferation and differentiation through the transcription of target genes. Compared with their levels in G1, activation of the receptor LRP6 and cytosolic β-catenin are both upregulated in G2 cells. However, accumulation of the Wnt pathway negative regulator AXIN2 also occurs in this phase. Therefore, it is unclear whether Wnt signaling is active in G2 phase cells. Here, we established a bimolecular fluorescence complementation (BiFC) biosensor system for the direct visualization of the β-catenin-TCF interaction in living cells. Using the BiFC biosensor and co-immunoprecipitation experiments, we demonstrate that levels of the nucleus-localized β-catenin-TCF complex increase during the S and G2 phases, and declines in the next G1 phase. Accordingly, a subset of Wnt target genes is transcribed by the β-catenin-TCF complex during both the S and G2 phases. By contrast, transient inhibition of this complex disturbs both cell survival and G2/M progression. Our results suggest that in S and G2 phase cells, Wnt-β-catenin signaling is highly active and functions to ensure cell survival and cell cycle progression.
authors.affiliation: MOE Key Laboratory of Protein Science, School of Life Sciences, Tsinghua University, Beijing 100084, China.
authors.forename: Yajie
authors.initials: Y
authors.lastname: Ding
authors.affiliation: MOE Key Laboratory of Protein Science, School of Life Sciences, Tsinghua University, Beijing 100084, China.
authors.forename: Shang
authors.initials: S
authors.lastname: Su
authors.affiliation: MOE Key Laboratory of Protein Science, School of Life Sciences, Tsinghua University, Beijing 100084, China.
authors.forename: Weixin
authors.initials: W
authors.lastname: Tang
authors.affiliation: MOE Key Laboratory of Protein Science, School of Life Sciences, Tsinghua University, Beijing 100084, China.
authors.forename: Xiaolei
authors.initials: X
authors.lastname: Zhang
authors.affiliation: MOE Key Laboratory of Protein Science, School of Life Sciences, Tsinghua University, Beijing 100084, China.
authors.forename: Shengyao
authors.initials: S
authors.lastname: Chen
authors.affiliation: MOE Key Laboratory of Protein Science, School of Life Sciences, Tsinghua University, Beijing 100084, China.
authors.forename: Guixin
authors.initials: G
authors.lastname: Zhu
authors.affiliation: MOE Key Laboratory of Protein Science, School of Life Sciences, Tsinghua University, Beijing 100084, China.
authors.forename: Juan
authors.initials: J
authors.lastname: Liang
authors.affiliation: School of Life Sciences, Peking University, Beijing 100871, China.
authors.forename: Wensheng
authors.initials: W
authors.lastname: Wei
authors.affiliation: MOE Key Laboratory of Bioorganic Phosphorus Chemistry and Chemical Biology, Tsinghua-Peking Center for Life Sciences, Department of Chemistry, Tsinghua University, Beijing 100084, China.
authors.forename: Ye
authors.initials: Y
authors.lastname: Guo
authors.affiliation: MOE Key Laboratory of Bioorganic Phosphorus Chemistry and Chemical Biology, Tsinghua-Peking Center for Life Sciences, Department of Chemistry, Tsinghua University, Beijing 100084, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Liu
authors.affiliation: The State Key Laboratory of Biomembrane and Membrane Biotechnology, Tsinghua-Peking Center for Life Sciences, School of Life Sciences, Tsinghua University, Beijing 100084, China.
authors.forename: Ye-Guang
authors.initials: YG
authors.lastname: Chen
authors.affiliation: MOE Key Laboratory of Protein Science, School of Life Sciences, Tsinghua University, Beijing 100084, China wwu@mail.tsinghua.edu.cn.
authors.forename: Wei
authors.initials: W
authors.lastname: Wu
mesh_terms: D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000378:metabolism; D002470:Cell Survival / Q000502:physiology; D016195:G2 Phase / Q000502:physiology*; D015870:Gene Expression; D006367:HeLa Cells; D006801:Humans; D016196:S Phase / Q000502:physiology*; D015398:Signal Transduction; D014158:Transcription, Genetic; D015533:Transcriptional Activation; D051176:beta Catenin / Q000235:genetics / Q000378:metabolism*
chemical_list: C495270:CTNNB1 protein, human; D051176:beta Catenin
keywords: BiFC; Cell cycle; Cell survival; TCF; β-catenin