PXD046931-1

PXD046931 is an original dataset announced via ProteomeXchange.

Title	PARP5A and RNF146 phase separation restrains RIPK1-dependent necroptosis
Description	Phase 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.
HostingRepository	iProX
AnnounceDate	2023-11-14
AnnouncementXML	Submission_2023-11-13_22:57:14.220.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Bing Shan
SpeciesList	scientific name: Mus musculus; NCBI TaxID: 10090;
ModificationList	ubiquitination signature dipeptidyl lysine
Instrument	LTQ Orbitrap

Revision	Datetime	Status	ChangeLog Entry
0	2023-11-13 22:56:45	ID requested
⏵ 1	2023-11-13 22:57:14	announced

Dataset with its publication pending

submitter keyword: RNF146

Daichao Xu
contact affiliation	Shanghai institute of Organic Chemistry, Chinese Academy of Sciences
contact email	xudaichao@sioc.ac.cn
lab head
Bing Shan
contact affiliation	Shanghai institute of Organic Chemistry, Chinese Academy of Sciences
contact email	shanbing@sioc.ac.cn
dataset submitter

iProX dataset URI