Dataset Information

Redox Proteomics Analysis of Auranofin Exposed Ovarian Cancer Cells

ABSTRACT: The effects of Auranofin (AF) on protein expression and protein oxidation in A2780 cancer cells were explored through a robust investigative strategy based on joint expression proteomics and redox proteomics determinations. Bioinformatics analysis of the proteomics data supports the view that the most critical cellular changes elicited by AF treatment consist of thioredoxin reductase inhibition, alteration of the cell redox state, impairment of the mitochondrial functions, associated metabolic changes with conversion to a glycolytic phenotype, induction of ER stress. The occurrence of the above cellular changes was extensively validated by performing direct biochemical assays. Our data are consistent with the concept that AF produces its effects through a multitarget mechanism that mainly affects the redox metabolism and mitochondrial functions and results in severe ER stress. Results are discussed in the frame of the current mechanistic knowledge existing on AF.

INSTRUMENT(S): Q Exactive

ORGANISM(S): Homo Sapiens (human)

SUBMITTER: Giovanni Chiappetta

LAB HEAD: Joelle Vinh

PROVIDER: PXD028681 | Pride | 2022-05-19

REPOSITORIES: Pride

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Publications

Redox proteome analysis of auranofin exposed ovarian cancer cells (A2780).

Chiappetta Giovanni G Gamberi Tania T Faienza Fiorella F Limaj Xhesika X Rizza Salvatore S Messori Luigi L Filomeni Giuseppe G Modesti Alessandra A Vinh Joelle J

Redox biology 20220322

The effects of Auranofin (AF) on protein expression and protein oxidation in A2780 cancer cells were investigated through a strategy based on simultaneous expression proteomics and redox proteomics determinations. Bioinformatics analysis of the proteomics data supports the view that the most critical cellular changes elicited by AF treatment consist of thioredoxin reductase inhibition, alteration of the cell redox state, impairment of the mitochondrial functions, metabolic changes associated wit ...[more]

PMID: 35358852

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Project description:E3 ubiquitin ligases mediate the last step of the ubiquitination pathwayin the ubiquitin-proteasome system (UPS). By targeting transcriptional regulators for their turnover, E3s play a crucial role in every aspect of plant biology. In plants, SKP1/CULLIN1/F-BOX PROTEIN (SCF)-type E3 ubiquitin ligases are essential for the perception and signaling of several key hormones including auxins and jasmonates (JAs). F-box proteins, TRANSPORT INHIBITOR RESPONSE 1 (TIR1) and CORONATINE INSENSITIVE 1 (COI1) bind directly transcriptional repressors AUX/IAAs and JAZs in an auxin- and JAs-depending manner, respectively, which permits the perception of the hormones and transcriptional activation of signaling pathways. Redox modification of proteins mainly by S-nitrosation of cysteines via nitric oxide (NO) has emerged as a valued regulatory mechanism in physiological processes requiring its rapid and versatile integration. Previously, we demonstrated that TIR1 and ASK1 (Arabidopsis thaliana SKP1) are targets of S-nitrosation, and these (NO)-dependent post-translational modifications enhance protein-protein interactions, and positively regulate SCFTIR1 complex assembly and expression of auxin response genes. In this work, we provide evidence on the modulation of SCFCOI1 complex by different S-nitrosation events. We demonstrated that S-nitrosation of ASK1 Cys118 enhanced ASK1-COI1 protein-protein interaction. Overexpression of non-nitrosable ask1 mutant protein impaired the activation of JA-responsive genes mediated by SCFCOI1 illustrating the functional relevance of this redox-mediated regulation in planta. Additionally, in silico analysis positioned COI1 as a promising S-nitrosation target. The regulation of SCF components involved in hormonal perception by S- nitrosation may represent a key strategy to determine the precise time and site-dependent activation of each hormonal signaling pathway, and highlights NO as a pivotal molecular player in these scenarios.

Dataset Information

Redox Proteomics Analysis of Auranofin Exposed Ovarian Cancer Cells

Publications

Redox proteome analysis of auranofin exposed ovarian cancer cells (A2780).

Similar Datasets

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