ReferenceID 2172
Leukamenin E Induces K8/18 Phosphorylation and Blocks the Assembly of Keratin Filament Networks Through ERK Activation
Int J Mol Sci
Leukamenin E is a natural ent-kaurane diterpenoid isolated from Isodon racemosa (Hemsl) Hara that has been found to be a novel and potential keratin filament inhibitor, but its underlying mechanisms remain largely unknow
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Record Fields
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- Reference Id
- 2172
- Evidence Id
- 18762
- Core Evidence Id
- 18762
- Source Reference Id
- 4398
- Herb2 Reference Id
- HBREF005195
- Subject Paper Key
- HBIN032987_32365802
- Pubmed Id
- 32365802
- Doi
- 10.3390/ijms21093164
- Paper Title
- Leukamenin E Induces K8/18 Phosphorylation and Blocks the Assembly of Keratin Filament Networks Through ERK Activation
- Paper Abstract
- Leukamenin E is a natural ent-kaurane diterpenoid isolated from Isodon racemosa (Hemsl) Hara that has been found to be a novel and potential keratin filament inhibitor, but its underlying mechanisms remain largely unknown. Here, we show that leukamenin E induces keratin filaments (KFs) depolymerization, largely independently of microfilament (MFs) and microtubules (MTs) in well-spread cells and inhibition of KFs assembly in spreading cells. These effects are accompanied by keratin phosphorylation at K8-Ser73/Ser431 and K18-Ser52 via the by extracellular signal-regulated kinases (ERK) pathway in primary liver carcinoma cells (PLC) and human umbilical vein endothelial cells (HUVECs). Moreover, leukamenin E increases soluble pK8-Ser73/Ser431, pK18-Ser52, and pan-keratin in the cytoplasmic supernatant by immunofluorescence imaging and Western blotting assay. Accordingly, leukamenin E inhibits the spreading and migration of cells. We propose that leukamenin E-induced keratin phosphorylation may interfere with the initiation of KFs assembly and block the formation of a new KFs network, leading to the inhibition of cell spreading. Leukamenin E is a potential target drug for inhibition of KFs assembly.
- Journal
- Int J Mol Sci
- Publish Year
- 2020
- Experiment Subject
- human; human umbilical vein endothelial cells; huvecs
- Experiment Type
- Cell Experiment
- Phenotype Related
- Liver Carcinoma
- Paper Title Cn
- Paper Title En
- Leukamenin E Induces K8/18 Phosphorylation and Blocks the Assembly of Keratin Filament Networks Through ERK Activation
- Bilingual Status
- semi_complete