PXD037373

PXD037373 is an original dataset announced via ProteomeXchange.

Title	Typhoid toxin hijacks Wnt5a to potentiate TGFβ-mediated senescence and Salmonella infection
Description	Damage to our genome causes acute senescence in mammalian cells, which undergo growth arrest and release a secretome that elicits cell cycle arrest in bystander cells through the senescence-associated secretory phenotype (SASP). Thus, acute senescence is a powerful tumour suppressor. Salmonella enterica hijacks senescence through its typhoid toxin, which usurps unidentified factors in the stress secretome of senescent cells to mediate intracellular infections. Here, transcriptomics of toxin-induced senescent cells (txSCs) and proteomics of their secretome identified secreted ligands that activate the TGFβ pathway through SMAD transcription factors. The ligand Wnt5a established a self-amplifying positive feedback loop driving TGFβ signalling, which enforced autocrine senescence in txSCs and paracrine senescence in naive bystander cells by activation of DDRs. Wnt5a and GDF15 increased host cell susceptibility to infection. The study reveals how an innate defence against cancer is co-opted by a bacterial pathogen to cause widespread damage and mediate infections.
HostingRepository	PRIDE
AnnounceDate	2024-10-22
AnnouncementXML	Submission_2024-10-22_06:02:48.311.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Mark Collins
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	monohydroxylated residue; iodoacetamide derivatized residue
Instrument	LTQ Orbitrap Elite

Revision	Datetime	Status	ChangeLog Entry
0	2022-10-13 14:37:22	ID requested
1	2023-09-07 04:43:13	announced
⏵ 2	2024-10-22 06:02:48	announced	2024-10-22: Updated project metadata.

Dataset with its publication pending

submitter keyword: Salmonella enterica, senescence, secretome

Mark Collins
contact affiliation	School of Biosciences University of Sheffield Firth Court, Western Bank Sheffield, S10 2TN United Kingdom
contact email	mark.collins@sheffield.ac.uk
lab head
Mark Collins
contact affiliation	University of Sheffield
contact email	mark.collins@sheffield.ac.uk
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD037373
     1. Label: PRIDE project
     2. Name: Typhoid toxin hijacks Wnt5a to potentiate TGFβ-mediated senescence and Salmonella infection