PXD017144

PXD017144 is an original dataset announced via ProteomeXchange.

Title	Antagonistic regulation of apoptosis by polysulfides and thioredoxin via persulfidation of caspases
Description	Hydrogen sulfide has been implicated in a large number of physiological processes including cell survival and death, encouraging research into its mechanisms of action and therapeutic potential. Recent studies suggest that the cellular effects of hydrogen sulfide are mediated in part by sulfane sulfur species including persulfides and polysulfides. In the present study, we investigated the apoptosis-modulating effects of polysulfides, in particular, in relation to the caspase cascade that mediates the intrinsic apoptotic pathway. Biochemical analyses revealed that organic or synthetic polysulfides strongly and rapidly inhibited the enzymatic activity of caspase-3, a major effector protease in apoptosis. Enzyme inhibition was attributed to persulfidation of the catalytic cysteine. In apoptotically stimulated HeLa cells, short-term exposure to polysulfides triggered the persulfidation and deactivation of cleaved caspae-3. These effects were antagonized by the thioredoxin/thioredoxin reductase system (Trx/TrxR). Indeed, Trx/TrxR restored the activity of polysulfide-inactivated caspase-3 in vitro, and inhibition of TrxR potentiated polysulfidemediated suppression of caspase-3 activity in situ. We further found that under conditions of low TrxR activity, early cell exposure to polysulfides lead to enhanced persulfidation of initiator caspase-9, resulting in decreased apoptosis. Beyond these observations, we show that the proenzymes, procaspase-3/-9, are basally persulfidated in resting (unstimulated) cells and become depersulfidated during their processing and activation. Inhibition of TrxR attenuated the depersulfidation and activation of caspase-9. Taken together, our results reveal that polysulfides target the caspase-9/3 cascade to suppress cancer cell apoptosis. The findings further suggest that Trx/TrxR-mediated depersulfidation may regulate caspase-dependent cell death.
HostingRepository	PRIDE
AnnounceDate	2020-02-18
AnnouncementXML	Submission_2020-02-18_08:05:16.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Tamar Ziv
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	sulfated residue; dehydrated residue; monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2020-01-16 02:01:37	ID requested
⏵ 1	2020-02-18 08:05:18	announced

Braunstein I, Engelman R, Yitzhaki O, Ziv T, Galardon E, Benhar M, Opposing effects of polysulfides and thioredoxin on apoptosis through caspase persulfidation. J Biol Chem, 295(11):3590-3600(2020) [pubmed]

submitter keyword: Polysulfides, caspases, apoptosis, persulfidation, thioredoxin

Moran Benhar
contact affiliation	Department of Biochemistry, Rappaport Institute for Research in the Medical Sciences, Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel
contact email	benhar@tx.technion.ac.il
lab head
Tamar Ziv
contact affiliation	Technion
contact email	tamarz@tx.technion.ac.il
dataset submitter

Dataset FTP location NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2020/02/PXD017144

PRIDE project URI

• PRIDE
  1. PXD017144
     1. Label: PRIDE project
     2. Name: Antagonistic regulation of apoptosis by polysulfides and thioredoxin via persulfidation of caspases