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Depression: 21st Century Solutions + The Dark Side of Wheat

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Abstract Title:

The plant sesquiterpene lactone parthenolide inhibits Wnt/β-catenin signaling by blocking synthesis of the transcriptional regulators TCF4/LEF1.

Abstract Source:

J Biol Chem. 2018 Apr 6 ;293(14):5335-5344. Epub 2018 Feb 9. PMID: 29462785

Abstract Author(s):

Xiaoliang Zhu, Chunmao Yuan, Chenyang Tian, Chen Li, Fen Nie, Xiaomin Song, Rong Zeng, Dianqing Wu, Xiaojiang Hao, Lin Li

Article Affiliation:

Xiaoliang Zhu

Abstract:

The Wnt/β-catenin pathway is essential for embryonic development and homeostasis, but excessive activation of this pathway is frequently observed in various human diseases, including cancer. Current therapeutic drugs targeting the Wnt pathway often lack sufficient efficacy, and new compounds targeting thispathway are therefore greatly needed. Here we report that the plant-derived natural product parthenolide (PTL), a sesquiterpene lactone, inhibits Wnt signaling. We found that PTL dose-dependently inhibits Wnt3a- and CHIR99021-induced transcriptional activity assessed with the T-cell factor (TCF)/lymphoid enhancer factor (LEF) firefly luciferase (TOPFlash) assay in HEK293 cells. Further investigations revealed that PTL decreases the levels of the transcription factors TCF4/LEF1 without affecting β-catenin stability or subcellular distribution. Moreover, this effect of PTL on TCF4/LEF1 was related to protein synthesis rather than to proteasome-mediated degradation. Of note, siRNA-mediated knockdown of RPL10, a ribosome protein PTL binds, substantially decreased TCF4/LEF1 protein levels and also Wnt3a-induced TOPFlash activities, suggesting a potential mechanism by which PTL may repress Wnt/β-catenin signaling. In summary, PTL binds RPL10 and thereby potently inhibits the Wnt/β-catenin pathway.

Study Type : In Vitro Study

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Sayer Ji
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Depression: 21st Century Solutions + The Dark Side of Wheat

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