PXD015537-1

PXD015537 is an original dataset announced via ProteomeXchange.

Title	Oligomerisation-driven MLKL ubiquitylation antagonises necroptosis
Description	Mixed lineage kinase domain-like (MLKL) is the executioner in the caspase 8-independent form of programmed cell death called necroptosis. Once Receptor Interacting serine/threonine Protein Kinase 3 (RIPK3) is activated by upstream cell death signals, it phosphorylates MLKL and triggers the oligomerization and membrane translocation required for MLKL induced membrane disruption. Besides phosphorylation, MLKL also undergoes ubiquitylation during the early stages of necroptosis, yet neither the mechanism nor the significance of this event has been demonstrated. Here we show that necroptosis-specific, multi-mono-ubiquitylation of MLKL occurs on biological membranes, and requires its activation and oligomerisation. Inactive MLKL mutants recruited to membranes during necroptosis are ubiquitylated but this results in their proteasome and lysosome dependent turnover. We identified several ubiquitylated lysines however mutation of these did not affect MLKL ubiquitylation in response to a necroptotic stimulus.
HostingRepository	PRIDE
AnnounceDate	2021-04-28
AnnouncementXML	Submission_2021-04-27_22:57:23.304.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Laura Dagley
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	ubiquitination signature dipeptidyl lysine; phosphorylated residue; monohydroxylated residue; acetylated residue; iodoacetamide derivatized residue
Instrument	Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2019-09-23 01:32:04	ID requested
⏵ 1	2021-04-27 22:57:23	announced
2	2024-10-22 05:21:28	announced	2024-10-22: Updated project metadata.

Dataset with its publication pending

submitter keyword: Membranes, MLKL, necroptosis, oligomerisation, ubiquitylation

John Silke
contact affiliation	Laboratory Head, Walter and Eliza Hall Institute, Australia
contact email	silke@wehi.edu.au
lab head
Laura Dagley
contact affiliation	WEHI
contact email	dagley.l@wehi.edu.au
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD015537
     1. Label: PRIDE project
     2. Name: Oligomerisation-driven MLKL ubiquitylation antagonises necroptosis