PXD038965

PXD038965 is an original dataset announced via ProteomeXchange.

Title	TRP14 is the rate limiting enzyme for intracellular cystine reduction and regulates proteome cysteinylation. 42 proteins showed higher cysteinylation levels in TRP14 knockdown cells compared to wild-type cells upon biotinylated cysteine incubation and subsequent streptavidin pulldown. Figure 2C.
Description	It has remained unknown how cells reduce cystine taken up from the extracellular space, which is a required step for further utilization of cysteine in key processes such as protein or glutathione synthesis. Here we show that the thioredoxin-related protein of 14 kDa (TRP14, encoded by TXNDC17) is the rate limiting enzyme for intracellular cystine reduction. When TRP14 is genetically knocked out, cysteine synthesis through the transsulfuration pathway becomes the major source of cysteine in human cells, and knockout of both pathways becomes lethal in C. elegans subjected to proteostatic stress. TRP14 can also reduce cysteinyl moieties on proteins, rescuing their activities as here shown with cysteinylated peroxiredoxin 2. Txndc17 knock-out mice were, surprisingly, protected in an acute pancreatitis model, concomitant with activation of Nrf2-driven antioxidant pathways and upregulation of transsulfuration. We conclude that TRP14 is the evolutionary conserved enzyme principally responsible for intracellular cystine reduction in C. elegans, mice and humans.
HostingRepository	PRIDE
AnnounceDate	2024-06-05
AnnouncementXML	Submission_2024-06-04_23:59:39.080.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Luz Valero
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	cysteinylation (disulfide with free L-cysteine)
Instrument	TripleTOF 5600

Revision	Datetime	Status	ChangeLog Entry
0	2022-12-20 06:52:23	ID requested
⏵ 1	2024-06-04 23:59:39	announced

Dataset with its publication pending

submitter keyword: thioredoxin,pancreatitis, cysteinylation, BODIPY

Juan Sastre
contact affiliation	Department of Physiology, Faculty of Pharmacy, University of Valencia, Burjassot, Valencia, Spain
contact email	juan.sastre@uv.es
lab head
Luz Valero
contact affiliation	Universitat de Valencia
contact email	mluz.valero@uv.es
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD038965
     1. Label: PRIDE project
     2. Name: TRP14 is the rate limiting enzyme for intracellular cystine reduction and regulates proteome cysteinylation. 42 proteins showed higher cysteinylation levels in TRP14 knockdown cells compared to wild-type cells upon biotinylated cysteine incubation and subsequent streptavidin pulldown. Figure 2C.