Pentabromopseudilin: a myosin V inhibitor suppresses TGF-β activity by recruiting the type II TGF-β receptor to lysosomal degradation

Journal of Enzyme Inhibition and Medicinal Chemistry
Wang Shih-WeiChun-Lin Chen

Abstract

Pentabromopseudilin (PBrP) is a marine antibiotic isolated from the marine bacteria Pseudomonas bromoutilis and Alteromonas luteoviolaceus. PBrP exhibits antimicrobial, anti-tumour, and phytotoxic activities. In mammalian cells, PBrP is known to act as a reversible and allosteric inhibitor of myosin Va (MyoVa). In this study, we report that PBrP is a potent inhibitor of transforming growth factor-β (TGF-β) activity. PBrP inhibits TGF-β-stimulated Smad2/3 phosphorylation, plasminogen activator inhibitor-1 (PAI-1) protein production and blocks TGF-β-induced epithelial-mesenchymal transition in epithelial cells. PBrP inhibits TGF-β signalling by reducing the cell-surface expression of type II TGF-β receptor (TβRII) and promotes receptor degradation. Gene silencing approaches suggest that MyoVa plays a crucial role in PBrP-induced TβRII turnover and the subsequent reduction of TGF-β signalling. Because, TGF-β signalling is crucial in the regulation of diverse pathophysiological processes such as tissue fibrosis and cancer development, PBrP should be further explored for its therapeutic role in treating fibrotic diseases and cancer.

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Citations

Aug 15, 2019·International Journal of Molecular Sciences·Chih-Ling ChungChun-Lin Chen
Oct 21, 2018·Scientific Reports·Kristen E WhalenElizabeth L Harvey
Dec 20, 2020·Biomedicine & Pharmacotherapy = Biomédecine & Pharmacothérapie·Cheng-Yi HuangChun-Lin Chen
Mar 2, 2021·Phytomedicine : International Journal of Phytotherapy and Phytopharmacology·Shu-Fang HuangChun-Lin Chen
Mar 7, 2021·Cancers·Nayden G NaydenovAndrei I Ivanov
Mar 7, 2021·Biomolecules·Roberta MelchionnaPaola Nisticò

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Methods Mentioned

BETA
nuclear translocation
protein
Protein Assay
transfection
Nuclear
confocal microscopy
affinity purification
density gradient fractionation
antisense oligonucleotides

Software Mentioned

ImageQuant
SPSS
ImageJ

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