Bryostatin-1에 의한 Wnt/β-Catenin 신호전달체계 저해효과
Suppression of the Wnt/β-catenin Pathway by Bryostatin-1
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The Wnt/β-catenin pathway plays important roles in a variety of biological processes, such as cell proliferation, differentiation,and organ development. Here, we used a cell-based reporter assay to identify bryostatin-1, a natural macrocyclic lactone, asan inhibitor of the Wnt/β-catenin pathway. Bryostatin-1 suppressed β-catenin response transcription (CRT), which was activatedby a Wnt3a-conditioned medium (Wnt3a-CM), through a decrease in the intracellular β-catenin protein levels, withoutaffecting its mRNA level. In addition, pharmacological inhibition of proteasome abrogated bryostatin-1-mediated down-regulationof the β-catenin protein level. Our findings suggest that bryostatin-1 attenuates the Wnt/β-catenin pathway through the promotionof proteasomal degradation of β-catenin.
Abstract
The Wnt/β-catenin pathway plays important roles in a variety of biological processes, such as cell proliferation, differentiation,and organ development. Here, we used a cell-based reporter assay to identify bryostatin-1, a natural macrocyclic lactone, asan inhibitor of the Wnt/β-catenin pathway. Bryostatin-1 suppressed β-catenin response transcription (CRT), which was activatedby a Wnt3a-conditioned medium (Wnt3a-CM), through a decrease in the intracellular β-catenin protein levels, withoutaffecting its mRNA level. In addition, pharmacological inhibition of proteasome abrogated bryostatin-1-mediated down-regulationof the β-catenin protein level. Our findings suggest that bryostatin-1 attenuates the Wnt/β-catenin pathway through the promotionof proteasomal degradation of β-catenin.
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