Dataset Information

Characterization of RAS/RAF/ERK signal cascade as a novel regulating factor in alpha-amanitin-induced liver injury

ABSTRACT: The well-known hepatotoxicity mechanism resulting from alpha-amanitin (-AMA) exposure arises from RNA polymerase II (RNAP II) inhibition. RNAP Ⅱ inhibition occurs through the dysregulation of mRNA synthesis. However, the signaling pathways in hepatocytes that arise from -AMA have not yet been fully elucidated. Here, we identified that the RAS/RAF/ERK signaling pathway was activated through quantitative phosphoproteomic and molecular biological analyses. Bioinformatics analysis showed that AMA exposure increased protein phosphorylation in a time-dependent AMA AMA exposure. In addition, phosphorylation increased not only the components of the ERK signaling pathway but also U2AF65 and SPF45, known splicing factors. Therefore, we propose a novel mechanism of -AMA as follows. The RAS/RAF/ERK signaling pathway involved in aberrant splicing events is activated by -AMA exposure followed by aberrant splicing events leading to cell death.

INSTRUMENT(S): LTQ Orbitrap Velos

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Hepatocyte

SUBMITTER: Doeun Kim

LAB HEAD: Sangkyu Lee

PROVIDER: PXD035817 | Pride | 2023-03-11

REPOSITORIES: Pride

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Dataset's files

Source:

			Action	DRS
	20210514_easynano50cm_3hr_30min_Huh7_5uM_AMA_0_12h_TMT_phospho_1_1.raw	Raw
	20210514_easynano50cm_3hr_30min_Huh7_5uM_AMA_0_12h_TMT_phospho_1_2.raw	Raw
	20210514_easynano50cm_3hr_30min_Huh7_5uM_AMA_0_12h_TMT_phospho_2_1.raw	Raw
	20210514_easynano50cm_3hr_30min_Huh7_5uM_AMA_0_12h_TMT_phospho_2_2.raw	Raw
	Uniprot_human_20181213.fasta	Fasta

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Publications

Characterization of the RAS/RAF/ERK Signal Cascade as a Novel Regulating Factor in Alpha-Amanitin-Induced Cytotoxicity in Huh-7 Cells.

Kim Doeun D Lee Min Seo MS Sung Eunji E Lee Sangkyu S Lee Hye Suk HS

International journal of molecular sciences 20221014 20

The well-known hepatotoxicity mechanism resulting from alpha-amanitin (α-AMA) exposure arises from RNA polymerase II (RNAP II) inhibition. RNAP Ⅱ inhibition occurs through the dysregulation of mRNA synthesis. However, the signaling pathways in hepatocytes that arise from α-AMA have not yet been fully elucidated. Here, we identified that the RAS/RAF/ERK signaling pathway was activated through quantitative phosphoproteomic and molecular biological analyses in Huh-7 cells. Bioinformatics analysis s ...[more]

PMID: 36293151

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