PXD021366-1

PXD021366 is an original dataset announced via ProteomeXchange.

Title	Phosphoproteome profiling uncovers a key role for CDKs in TNF signaling
Description	Tumor necrosis factor (TNF) is one of the few cytokines successfully targeted by therapies against inflammatory diseases. However, blocking this well studied and pleiotropic ligand can cause dramatic side-effects. We reasoned that a systems-level proteomic analysis of TNF signaling could dissect its diverse functions and offer a base for developing more targeted therapies. Combining phosphoproteomics time course experiments with spatial and kinase inhibitor analysis clusters phosphorylations into functional modules. The majority of regulated phosphorylations could be assigned to an upstream kinase by inhibiting master kinases and spatial proteomics revealed phosphorylation-dependent translocations of hundreds of proteins upon TNF stimulation. Phosphoproteome analysis of TNF-induced apoptosis and necroptosis revealed a key role for transcriptional cyclin-dependent kinase (CDK) activity to promote cytokine production and prevent excessive cell death downstream of the TNF signaling receptor. Our comprehensive interrogation of TNF induced pathways and sites can be explored at http://tnfviewer.biochem.mpg.de/.
HostingRepository	PRIDE
AnnounceDate	2021-10-11
AnnouncementXML	Submission_2021-10-11_04:30:05.473.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Mario Oroshi
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090; scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	phosphorylated residue
Instrument	Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2020-09-09 01:03:28	ID requested
⏵ 1	2021-10-11 04:30:05	announced

Dataset with its publication pending

submitter keyword: TNF, phosphoproteomics, cell death, spatial proteomics, apoptosis, necroptosis, Cyclin-dependent kinases, transcription, spatial proteomics, kinases

Matthias Mann
contact affiliation	Department of Proteomics and Signal Transduction Max Planck Institute of Biochemistry Germany
contact email	mmann@biochem.mpg.de
lab head
Mario Oroshi
contact affiliation	Proteomics
contact email	oroshi@biochem.mpg.de
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD021366
     1. Label: PRIDE project
     2. Name: Phosphoproteome profiling uncovers a key role for CDKs in TNF signaling