PXD059944

PXD059944 is an original dataset announced via ProteomeXchange.

Title	Acrolein attached mouse cell LC-MS/MS
Description	Dysregulated cell death leading to uncontrolled cell proliferation is a major hallmark of cancer. Chemotherapy-induced cell death is critical for the success of cancer treatment but this process is impaired by metabolic byproducts. How these metabolic byproducts interfere with the efficacies of anti-cancer therapy is unclear. Here, we show that the metabolic byproduct acrolein derived from polyamine metabolic pathways, tobacco smoke or fuel combustion, induces ferroptosis independently of the immune sensor ZBP1, inflammasomes and type I IFN signaling. In addition, acrolein suppresses necroptosis in cancer cells by inhibiting the oligomerization of the necroptosis effector MLKL. Loss of SAT1, a key enzyme in polyamine metabolism responsible for intracellular acrolein production, sensitizes cells to necroptosis. In tumor xenograft models, administration of an acrolein-trapping agent in mice, to remove acrolein and relieve necroptosis blockade, enhances the therapeutic efficacy of the chemotherapeutic agent cyclophosphamide. In humans, patients with high cell death activity but low expression of polyamine metabolism-related genes exhibit improved survival. These findings highlight that the removal of toxic metabolic byproducts that block necroptosis improves the success of certain chemotherapies.
HostingRepository	PRIDE
AnnounceDate	2025-05-13
AnnouncementXML	Submission_2025-05-13_03:45:15.598.xml
DigitalObjectIdentifier	https://dx.doi.org/10.6019/PXD059944
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Supported dataset by repository
PrimarySubmitter	Jaemin Lim
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Orbitrap Exploris 480

Revision	Datetime	Status	ChangeLog Entry
0	2025-01-19 17:19:03	ID requested
⏵ 1	2025-05-13 03:45:15	announced

10.6019/PXD059944;

submitter keyword: mouse, cell, acrolein, LC-MS/MS

Rajendra Karki
contact affiliation	Department of Biological Sciences, College of Natural Sciences, Seoul National University, Seoul, 08826, Republic of Korea
contact email	rkarki@snu.ac.kr
lab head
Jaemin Lim
contact affiliation	Kyung Hee Univiersity
contact email	jami1031@khu.ac.kr
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD059944
     1. Label: PRIDE project
     2. Name: Acrolein attached mouse cell LC-MS/MS