PXD051840

PXD051840 is an original dataset announced via ProteomeXchange.

Title	Revealing disulfide bond formation in GSDME upon UVC irradiation under non-reducing conditions
Description	It is widely acknowledged that gasdermin family proteins, which are known as the executors of pyroptosis, undergo protease-mediated cleavage prior to inducing pyroptosis. Here, we unexpectedly discovered a non-canonical form of pyroptosis mediated by full-length GSDME (FL-GSDME) without any proteolytic cleavage. Upon intense ultraviolet (UV) irradiation-triggered DNA damage, hyperactivation of nuclear PARP1 led to extensive formation of poly(ADP-ribose) (PAR) polymers and then release to the cytoplasm.These PAR polymers activate PARP5 to catalyze GSDME PARylation, resulted in a conformational change in GSDME that relieved autoinhibition imposed by its C terminus on the N terminus. On the other hand, intense UV irradiation boosted mitochondrial fission-dependent generation of mitochondrial reactive oxygen species (mito-ROS), further promoting cytochrome c-catalyzed peroxidation of cardiolipin. This lipid-ROS signal was then sensed by PARylated-GSDME and then induced oxidative oligomerization of GSDME, which facilitated FL-GSDME plasma membrane targeting for perforation, eventually inducing pyroptosis. Reagents that concurrently stimulate PARPs activity and lipid-ROS also induced sequential modifications i.e., PARylation and oxidation of FL-GSDME and synergistically promoted pyroptotic cell death. Overall, our findings elucidate a novel mechanism underlying cleavage-independent function of GSDME in executing cell demise, further enriching the paradigms and cognition of FL-GSDME-mediated non-canonical pyroptosis.
HostingRepository	PRIDE
AnnounceDate	2024-06-17
AnnouncementXML	Submission_2024-06-16_18:00:04.694.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Bo Zhou
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	monohydroxylated residue
Instrument	Orbitrap Fusion Lumos

Revision	Datetime	Status	ChangeLog Entry
0	2024-04-29 10:12:59	ID requested
⏵ 1	2024-06-16 18:00:05	announced

Dataset with its publication pending

submitter keyword: UVC;GSDME;Disulfide bond

Hang-zi Chen
contact affiliation	State Key Laboratory of Cellular Stress Biology, School of Life Sciences, Xiamen University, Xiamen, Fujian 361102, China
contact email	chenhz@xmu.edu.cn
lab head
Bo Zhou
contact affiliation	School of Life Sciences, Xiamen University
contact email	1147321373@qq.com
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD051840
     1. Label: PRIDE project
     2. Name: Revealing disulfide bond formation in GSDME upon UVC irradiation under non-reducing conditions