PXD017144 is an
original dataset announced via ProteomeXchange.
Dataset Summary
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 | 2024-10-22 |
AnnouncementXML | Submission_2024-10-22_05:00:27.923.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 |
Dataset History
Revision | Datetime | Status | ChangeLog Entry |
0 | 2020-01-16 02:01:37 | ID requested | |
1 | 2020-02-18 08:05:18 | announced | |
⏵ 2 | 2024-10-22 05:00:32 | announced | 2024-10-22: Updated project metadata. |
Publication List
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] |
10.1074/jbc.ra119.012357; |
Keyword List
submitter keyword: thioredoxin, persulfidation,Polysulfides, apoptosis, caspases |
Contact List
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 | |
Full Dataset Link List
Dataset FTP location
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PRIDE project URI |
Repository Record List
[ + ]
[ - ]
- PRIDE
- PXD017144
- Label: PRIDE project
- Name: Antagonistic regulation of apoptosis by polysulfides and thioredoxin via persulfidation of caspases