Interaction and functional cooperation between the LIM protein FHL2, CBP/p300, and beta-catenin.
Transcriptional activation of gene expression by Wnt signaling is driven by the association of beta-catenin with TCF/LEF factors and the recruitment of transcriptional coactivators. It has been shown that the LIM protein FHL2 and the acetyltransferase CBP/p300 individually stimulate beta-catenin transactivating activity and that beta-catenin is acetylated by p300. Here, ... we report that FHL2 and CBP/p300 synergistically enhanced beta-catenin/TCF-mediated transcription from Wnt-responsive promoters and that the acetyltransferase activity of CBP/p300 was involved in the cooperation. CBP/p300 interacted directly with FHL2, predominantly through the CH3 domain but not the histone acetyltransferase domain, and different regions of CBP/p300 were involved in FHL2 and beta-catenin binding. We provided evidence for the formation of a ternary complex by FHL2, CBP/p300, and beta-catenin and for colocalization of the three proteins in the nucleus. In murine FHL2(-/-) embryo fibroblasts, the transactivation activity of beta-catenin/TCF was markedly reduced, and this defect could be restored by exogenous expression of FHL2. However, CBP/p300 were still able to coactivate the beta-catenin/TCF complex in FHL2(-/-) cells, suggesting that FHL2 is dispensable for the coactivator function of CBP/p300 on beta-catenin. Furthermore, we found that FHL2 significantly increased acetylation of beta-catenin by p300 in vivo. Finally, we showed that FHL2, CBP/p300, and beta-catenin could synergistically activate androgen receptor-mediated transcription, indicating that the synergistic coactivator function is not restricted to TCF/LEF.
Mesh Terms:
Acetylation, Animals, Baculoviridae, COS Cells, Cadherins, Cell Line, Cell Line, Tumor, Cell Nucleus, Cells, Cultured, Cercopithecus aethiops, Cytoskeletal Proteins, Embryo, Mammalian, Embryo, Nonmammalian, Fibroblasts, Glutathione Transferase, Homeodomain Proteins, Humans, Immunoblotting, LIM-Homeodomain Proteins, Luciferases, Muscle Proteins, Neoplasm Proteins, Precipitin Tests, Protein Structure, Tertiary, RNA, Receptors, Androgen, Recombinant Proteins, Spodoptera, Trans-Activators, Transcription Factors, Transcriptional Activation, Zinc Fingers, beta Catenin
Acetylation, Animals, Baculoviridae, COS Cells, Cadherins, Cell Line, Cell Line, Tumor, Cell Nucleus, Cells, Cultured, Cercopithecus aethiops, Cytoskeletal Proteins, Embryo, Mammalian, Embryo, Nonmammalian, Fibroblasts, Glutathione Transferase, Homeodomain Proteins, Humans, Immunoblotting, LIM-Homeodomain Proteins, Luciferases, Muscle Proteins, Neoplasm Proteins, Precipitin Tests, Protein Structure, Tertiary, RNA, Receptors, Androgen, Recombinant Proteins, Spodoptera, Trans-Activators, Transcription Factors, Transcriptional Activation, Zinc Fingers, beta Catenin
Mol. Cell. Biol.
Date: Dec. 01, 2004
PubMed ID: 15572674
View in: Pubmed Google Scholar
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