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PXD006055

PXD006055 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitleQuantitative Phospho-proteomic Analysis of TNFα/NFκB Signaling Reveals a Role for RIPK1 Phosphorylation in Suppressing Necrotic Cell Death
DescriptionTNFα is a potent inducer of inflammation due to its ability to promote gene expression, inpart via the NFκB pathway. Moreover, in some contexts, TNFα promotes Caspase-dependent apoptosis or RIPK1/RIPK3/MLKL-dependent necrosis. Engagement of the TNF Receptor Signaling Complex (TNF-RSC), which contains multiple kinase activities, promotes phosphorylation of several downstream components, including TAK1, IKKα/IKKβ, IκBα and NFκB. However, immediate downstream phosphorylation events occurring in response to TNFα signaling are poorly understood at a proteome-wide level. Here we use Tandem mass tagging-based proteomics to quantitatively characterize acute TNFα-mediated alterations in the proteome and phosphoproteome with or without inhibition of the cIAP-dependent survival arm of the pathway with a SMAC mimetic. We identify and quantify over 8,000 phosphorylated peptides, among which are numerous known sites in the TNF-RSC, NFκB, and MAP kinase signaling systems, as well as numerous previously unrecognized phosphorylation events. Functional analysis of S320 phosphorylation in RIPK1 demonstrates a role for this event in suppressing its kinase activity, association with CASPASE-8 and FADD proteins, and subsequent necrotic cell death during inflammatory TNFα stimulation. This study provides a resource for further elucidation of TNFα-dependent signaling pathways.
HostingRepositoryPRIDE
AnnounceDate2024-10-22
AnnouncementXMLSubmission_2024-10-22_04:08:38.563.xml
DigitalObjectIdentifier
ReviewLevelPeer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportUnsupported dataset by repository
PrimarySubmitterFiraz Mohideen
SpeciesList scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationListphosphorylated residue; monohydroxylated residue; iodoacetamide derivatized residue
InstrumentOrbitrap Fusion
Dataset History
RevisionDatetimeStatusChangeLog Entry
02017-03-08 06:19:19ID requested
12017-05-30 00:12:33announced
22024-10-22 04:08:39announced2024-10-22: Updated project metadata.
Publication List
10.1074/mcp.M117.068189;
Mohideen F, Paulo JA, Ordureau A, Gygi SP, Harper JW, B Signaling Reveals a Role for RIPK1 Phosphorylation in Suppressing Necrotic Cell Death. Mol Cell Proteomics, 16(7):1200-1216(2017) [pubmed]
Keyword List
curator keyword: Biological
submitter keyword: Inflammatory response, Cellular Signaling, Cell death,Mass spectrometry, Phosphoproteome
Contact List
Firaz Mohideen
contact affiliationHarvard Medical School
contact emailfiraz_mohideen@hms.harvard.edu
lab head
Firaz Mohideen
contact affiliationHarvard Medical School
contact emailFiraz_Mohideen@hms.harvard.edu
dataset submitter
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Dataset FTP location
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PRIDE project URI
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