PXD006055-1

PXD006055 is an original dataset announced via ProteomeXchange.

Title	Quantitative Phospho-proteomic Analysis of TNFα/NFκB Signaling Reveals a Role for RIPK1 Phosphorylation in Suppressing Necrotic Cell Death
Description	TNFα 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.
HostingRepository	PRIDE
AnnounceDate	2017-05-30
AnnouncementXML	Submission_2017-05-30_00:12:32.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Firaz Mohideen
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	phosphorylated residue; monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Orbitrap Fusion

Revision	Datetime	Status	ChangeLog Entry
0	2017-03-08 06:19:19	ID requested
⏵ 1	2017-05-30 00:12:33	announced
2	2024-10-22 04:08:39	announced	2024-10-22: Updated project metadata.

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]

curator keyword: Biological

submitter keyword: Mass spectrometry, Phosphoproteome, Cellular Signaling, Cell death, Inflammatory response

Firaz Mohideen
contact affiliation	Harvard Medical School
contact email	firaz_mohideen@hms.harvard.edu
lab head
Firaz Mohideen
contact affiliation	Harvard Medical School
contact email	Firaz_Mohideen@hms.harvard.edu
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD006055
     1. Label: PRIDE project
     2. Name: Quantitative Phospho-proteomic Analysis of TNFα/NFκB Signaling Reveals a Role for RIPK1 Phosphorylation in Suppressing Necrotic Cell Death