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PXD046931-1

PXD046931 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitlePARP5A and RNF146 phase separation restrains RIPK1-dependent necroptosis
DescriptionPhase separation is a vital mechanism that mediates the formation of biomolecular condensates and their functions. Necroptosis is a lytic form of programmed cell death mediated by RIPK1, RIPK3 and MLKL downstream of TNFR1 and other receptors and has been implicated in mediating many human diseases. However, whether necroptosis is regulated by phase separation is not yet known. Here, we show that upon the induction of necroptosis and recruitment by the adaptor protein TAX1BP1, PARP5A and its binding partner RNF146 are rapidly induced to form liquid-like condensates by multivalent interactions to perform poly ADP-ribosylation (PARylation) and PARylation-dependent ubiquitination (PARdU) of activated RIPK1. We show that PARdU predominantly occurs on the K376 residue of RIPK1, which promotes proteasomal degradation of kinase-activated RIPK1 to restrain the formation of necrosomes. This modification is essential in vivo, as PARP5A deficiency sensitized mice to TNFα-induced lethal shock in a RIPK1kinase-dependent manner. Our data demonstrate that PARdU on K376 RIPK1 provides an alternative cell death checkpoint mediated by phase separation-dependent control of necroptosis by PARP5A and RNF146.
HostingRepositoryiProX
AnnounceDate2023-11-14
AnnouncementXMLSubmission_2023-11-13_22:57:14.220.xml
DigitalObjectIdentifier
ReviewLevelPeer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportUnsupported dataset by repository
PrimarySubmitterBing Shan
SpeciesList scientific name: Mus musculus; NCBI TaxID: 10090;
ModificationListubiquitination signature dipeptidyl lysine
InstrumentLTQ Orbitrap
Dataset History
RevisionDatetimeStatusChangeLog Entry
02023-11-13 22:56:45ID requested
12023-11-13 22:57:14announced
Publication List
Dataset with its publication pending
Keyword List
submitter keyword: RNF146
Contact List
Daichao Xu
contact affiliationShanghai institute of Organic Chemistry, Chinese Academy of Sciences
contact emailxudaichao@sioc.ac.cn
lab head
Bing Shan
contact affiliationShanghai institute of Organic Chemistry, Chinese Academy of Sciences
contact emailshanbing@sioc.ac.cn
dataset submitter
Full Dataset Link List
iProX dataset URI