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Interplay of Fli-I and FLAP1 for regulation of β-catenin dependent transcription

By Young-Ho Lee and Michael R. Stallcup


β-catenin mediates Wnt/wingless signaling and transcriptional activation by lymphocyte enhancer binding factor 1/T cell factor (LEF1/TCF) proteins with the assistance of multiple coregulators, including positive cofactors like p300/CBP and negative cofactors like HDACs. We previously demonstrated that a developmentally essential protein, Flightless-I (Fli-I), serves as a coactivator for nuclear receptor-mediated transcription. To further understand the action mechanism of Fli-I, we investigated the functional roles of Fli-I and Fli-I leucine rich repeat associated protein 1 (FLAP1) in transcriptional activation by β-catenin and LEF1/TCF. β-catenin-dependent transcription was activated by exogenous FLAP1 but inhibited by Fli-I. Reduction of endogenous FLAP1 levels compromised transcriptional activation by LEF1/TCF, β-catenin and the p160 coactivator GRIP1. FLAP1 interacted directly with β-catenin, GRIP1 and p300 and enhanced their activity. Furthermore, FLAP1 was strongly synergistic with p300 in supporting transcriptional activation by β-catenin and LEF1/TCF, but Fli-I disrupted the synergy of FLAP1 with p300 and β-catenin. Thus the opposing effects of Fli-I and FLAP1 may be a key regulatory mechanism for β-catenin and LEF1/TCF-mediated transcription and thus for Wnt signaling, and some mutations of Fli-I may result in developmental defects, such as the flightless phenotype of Drosophila, by causing dysregulation of the Wnt/β-catenin pathway

Topics: Molecular Biology
Publisher: Oxford University Press
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Provided by: PubMed Central
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    1. (2004). An autocrine mechanism for constitutive Wnt pathway activation in human cancer cells.
    2. (2005). Arginine methyltransferase CARM1 is a promoter-specific regulator of NF-kappaB-dependent gene expression.
    3. (2006). Balancing cell adhesion and Wnt signaling, the key role of beta-catenin.
    4. (2000). Beta-catenin affects androgen receptor transcriptional activity and ligand specificity.
    5. (2003). Beta-catenin binds to the activation function 2 region of the androgen receptor and modulates the effects of the N-terminal domain and TIF2 on ligand-dependent transcription.
    6. (2000). Beta-catenin-histone deacetylase interactions regulate the transition of LEF1 from a transcriptional repressor to an activator.
    7. (2003). Caught up in a Wnt storm: Wnt signaling in cancer.
    8. (2003). Chibby, a nuclear beta-catenin-associated antagonist of the Wnt/Wingless pathway.
    9. (2000). Curbing the nuclear activities of beta-catenin. Control over Wnt target gene expression.
    10. (2004). Developmentally essential protein flightless I is a nuclear receptor coactivator with actin binding activity.
    11. (1998). Drosophila Tcf and Groucho interact to repress Wingless signalling activity.
    12. (1998). Identification of the binding partners for flightless I, A novel protein bridging the leucine-rich repeat and the gelsolin superfamilies.
    13. (2005). Identification of the Wnt signaling activator leucine-rich repeat in flightless interaction protein 2 by a genome-wide functional analysis.
    14. (2000). Mammalian homologues of the Drosophila melanogaster flightless I gene involved in early development.
    15. (1999). Novel proteins interacting with the leucine-rich repeat domain of human flightless-I identified by the yeast two-hybrid system.
    16. (2004). Ordered cooperative functions of PRMT1, p300, and CARM1 in transcriptional activation by p53.
    17. (2006). Redundant expression of canonical Wnt ligands in human breast cancer cell lines.
    18. (2000). Regulation of beta -catenin transformation by the p300 transcriptional coactivator.
    19. (2005). Regulation of coactivator complex assembly and function by protein arginine methylation and demethylimination.
    20. (2002). Synergistic coactivator function by coactivator-associated arginine methyltransferase (CARM) 1 and beta-catenin with two different classes of DNA-binding transcriptional activators.
    21. (2004). Synergistic effects of coactivators GRIP1 and beta-catenin on gene activation: cross-talk between androgen receptor and Wnt signaling pathways.
    22. (2000). Synergistic, p160 coactivator-dependent enhancement of estrogen receptor function by CARM1 and p300.
    23. (2002). Synergy among nuclear receptor coactivators: selective requirement for protein methyltransferase and acetyltransferase activities.
    24. (2001). The chromatin remodelling factor Brg-1 interacts with beta-catenin to promote target gene activation.
    25. (1993). The Drosophila melanogaster flightless-I gene involved in gastrulation and muscle degeneration encodes gelsolin-like and leucine-rich repeat domains and is conserved in Caenorhabditis elegans and humans.
    26. (2001). The flightless I protein colocalizes with actin- and microtubule-based structures in motile Swiss 3T3 fibroblasts: evidence for the involvement of PI 3-kinase and Ras-related small GTPases.
    27. (2000). The flightless I protein localizes to actin-based structures during embryonic development.
    28. (1995). The human homologue of the Drosophila melanogaster flightless-I gene (flil) maps within the Smith-Magenis microdeletion critical region in 17p11.2.
    29. (2001). The leucine-rich repeat as a protein recognition motif.
    30. (1999). The role of the androgen receptor in the development and progression of prostate cancer.
    31. (2003). The roles of protein-protein interactions and protein methylation in transcriptional activation by nuclear receptors and their coactivators.
    32. (2000). The transcriptional coactivator CBP interacts with beta-catenin to activate gene expression.
    33. (1998). The Xenopus Wnt effector XTcf-3 interacts with Groucho-related transcriptional repressors.
    34. (1998). Transcriptional repression by AML1 and LEF-1 is mediated by the TLE/Groucho corepressors.
    35. (1998). TRIP: a novel double stranded RNA binding protein which interacts with the leucine rich repeat of flightless I.
    36. (2004). Wnt/beta-catenin and estrogen signaling converge in vivo.
    37. (1999). XCtBP is a XTcf-3 co-repressor with roles throughout Xenopus development.

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