ArticleMolecular and cellular biology2012
A WNT/p21 circuit directed by the C-clamp, a sequence-specific DNA binding domain in TCFs.
Article in Molecular and cellular biology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.
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Who cites it
33 citing papers in PubMed, 46 citations in OpenAlex.
- Epigenomic characterization of locally advanced anal cancer: a radiation therapy oncology group 98-11 specimen study.Diseases of the colon and rectum · 2014Trial
- Differential Wnt/β-catenin signaling via TCF7L2/LEF1 binding specificity shapes cellular and tumor phenotypes.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Review
- Evolutionary diversification of the canonical Wnt signaling effector TCF/LEF in chordates.Development, growth & differentiation · 2022Article
- Wnt target enhancer regulation by a CDX/TCF transcription factor collective and a novel DNA motif.Nucleic acids research · 2021Article
- The WNT/β-catenin dependent transcription: A tissue-specific business.WIREs mechanisms of disease · 2021Review
- Intermittent hypoxia exacerbates tumor progression in a mouse model of lung cancer.Scientific reports · 2020Article
- Developmentally regulatedeLife · 2019Article
- Article
- Sp5 negatively regulates the proliferation of HCT116 cells by upregulating the transcription of p27.Oncology letters · 2018Article
- Article
- A new mode of DNA binding distinguishes Capicua from other HMG-box factors and explains its mutation patterns in cancer.PLoS genetics · 2017Article
- Mathematical modeling links Wnt signaling to emergent patterns of metabolism in colon cancer.Molecular systems biology · 2017Article
- ZNF395 Is an Activator of a Subset of IFN-Stimulated Genes.Mediators of inflammation · 2017Article
- Wnt target genes and where to find them.F1000Research · 2017Review
- Review
- Review
- Wnt/β-catenin and LIF-Stat3 signaling pathways converge on Sp5 to promote mouse embryonic stem cell self-renewal.Journal of cell science · 2016Article
- Regulation of the TMEPAI promoter by TCF7L2: the C-terminal tail of TCF7L2 is essential to activate the TMEPAI gene.Journal of biochemistry · 2016Article
- Lactate/pyruvate transporter MCT-1 is a direct Wnt target that confers sensitivity to 3-bromopyruvate in colon cancer.Cancer & metabolism · 2016Article
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
The lymphoid enhancer factor 1/T cell factor (LEF/TCF) family of transcription factors are downstream effectors of the WNT signaling pathway, which drives colon tumorigenesis. LEF/TCFs have a DNA sequence-specific high-mobility group (HMG) box that binds Wnt response elements (WREs). The "E tail" isoforms of TCFs are alternatively spliced to include a second DNA binding domain called the C-clamp. We show that induction of a dominant negative C-clamp version of TCF1 (dnTCF1E) induces p21 expression and a stall in the growth of DLD1 colon cancer cells. Induction of a C-clamp mutant did not efficiently induce p21, nor did it stall cell growth. Microarray analysis revealed that induction of p21 by wild-type dnTCF1E (dnTCF1E(WT)) correlated with a decrease in expression of multiple p21 suppressors that act at multiple levels from transcription (SP5, YAP1, and RUNX1), RNA stability (MSI2), and protein stability (CUL4A). We show that the C-clamp is a sequence-specific DNA binding domain that can make contacts with 5'-RCCG-3' elements upstream or downstream of WREs. The C-clamp-RCCG interaction was critical for TCF1E-mediated transcriptional control of p21-connected target gene promoters. Our results indicate that a rapid-response WNT/p21 circuit is driven by C-clamp target gene selection.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.