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
Mol. Cell. Biol.
Date: Dec. 01, 2004
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