Dataset Information

Cisplatin toxicity is counteracted by the activation of the p38/ATF-7 signaling pathway in post-mitotic C. elegans

ABSTRACT: Cisplatin kills proliferating cells via DNA damage but also has profound effects on post-mitotic cells in tumors, kidneys, and neurons. However, the effects of cisplatin on post-mitotic cells are still poorly understood. Among model systems, C. elegans adults are unique in having completely post-mitotic somatic tissues. The p38 MAPK pathway controls ROS detoxification via SKN-1/NRF and immune responses via ATF-7/ATF2. We show that p38 MAPK pathway mutants are sensitive to cisplatin, but while cisplatin exposure increases ROS levels, skn-1 mutants are resistant. Cisplatin exposure leads to phosphorylation of PMK-1/MAPK and ATF-7 and the IRE-1/TRF-1 signaling module functions upstream of the p38 MAPK pathway to activate signaling. We identify the response proteins whose increased abundance depends on IRE-1/p38 MAPK activity as well as cisplatin exposure. Four of these proteins are necessary for protection from cisplatin toxicity, which is characterized by necrotic death. We conclude that the p38 MAPK pathway-driven proteins are crucial for adult cisplatin resilience.

INSTRUMENT(S): Orbitrap Fusion

ORGANISM(S): Caenorhabditis Elegans

SUBMITTER: Proteomics Core Facility

LAB HEAD: Peter Naredi

PROVIDER: PXD033377 | Pride | 2023-04-26

REPOSITORIES: Pride

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Dataset's files

Source:

			Action	DRS
	3036_Sets_comb_norm_0miss_UniprotcelegansOnly.msf	Msf
	3036_Sets_comb_norm_0miss_UniprotcelegansOnly.pdResult	Other
	3036_TMTSets_combined_normalized_0miss_Uniprot_celegansOnly.xlsx	Xlsx
	3036_sequence_Fusion_181127.xlsx	Xlsx
	Fusion_181127_30.raw	Raw

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Publications

Cisplatin toxicity is counteracted by the activation of the p38/ATF-7 signaling pathway in post-mitotic C. elegans.

Raj Dorota D Kraish Bashar B Martikainen Jari J Podraza-Farhanieh Agnieszka A Kao Gautam G Naredi Peter P

Nature communications 20230520 1

Cisplatin kills proliferating cells via DNA damage but also has profound effects on post-mitotic cells in tumors, kidneys, and neurons. However, the effects of cisplatin on post-mitotic cells are still poorly understood. Among model systems, C. elegans adults are unique in having completely post-mitotic somatic tissues. The p38 MAPK pathway controls ROS detoxification via SKN-1/NRF and immune responses via ATF-7/ATF2. Here, we show that p38 MAPK pathway mutants are sensitive to cisplatin, but wh ...[more]

PMID: 37210583

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