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  Phosphoproteome profiling uncovers a key role for CDKs in TNF signaling

Tanzer, M. C., Bludau, I., Stafford, C. A., Hornung, V., & Mann, M. (2021). Phosphoproteome profiling uncovers a key role for CDKs in TNF signaling. Nature Communications, 12(1): 6053. doi:10.1038/s41467-021-26289-6.

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Open Access funding enabled and organized by Projekt DEAL.

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 Creators:
Tanzer, Maria C.1, Author           
Bludau, Isabell1, Author           
Stafford, Che A.2, Author
Hornung, Veit2, Author
Mann, Matthias1, Author           
Affiliations:
1Mann, Matthias / Proteomics and Signal Transduction, Max Planck Institute of Biochemistry, Max Planck Society, ou_1565159              
2external, ou_persistent22              

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Free keywords: NF-KAPPA-B; CELL-DEATH; P-TEFB; KINASE; PHOSPHORYLATION; ACTIVATION; NECROSIS; RIPK1; NECROPTOSIS; INHIBITIONScience & Technology - Other Topics;
 Abstract: Tumor necrosis factor (TNF) has various effects on phosphorylation-mediated cellular signaling. Combining phosphoproteomics, subcellular localization analyses and kinase inhibitor assays, the authors provide systems level insights into TNF signaling and identify modulators of TNF-induced cell death.
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. Here, we reason that a systems-level proteomic analysis of TNF signaling could dissect its diverse functions and offer a base for developing more targeted therapies. Therefore, we combine phosphoproteomics time course experiments with subcellular localization and kinase inhibitor analysis to identify functional modules of protein phosphorylation. The majority of regulated phosphorylation events can be assigned to an upstream kinase by inhibiting master kinases. Spatial proteomics reveals phosphorylation-dependent translocations of hundreds of proteins upon TNF stimulation. Phosphoproteome analysis of TNF-induced apoptosis and necroptosis uncovers a key role for transcriptional cyclin-dependent kinase activity to promote cytokine production and prevent excessive cell death downstream of the TNF signaling receptor. This resource of TNF-induced pathways and sites can be explored at .

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Language(s): eng - English
 Dates: 2021
 Publication Status: Published online
 Pages: 15
 Publishing info: -
 Table of Contents: -
 Rev. Type: -
 Degree: -

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Project name : Marie Skłodowska-Curie Grant Agreement
Grant ID : 754388
Funding program : Horizon 2020 (H2020)
Funding organization : European Commission (EC)

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Title: Nature Communications
  Abbreviation : Nat. Commun.
Source Genre: Journal
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Publ. Info: London : Nature Publishing Group
Pages: - Volume / Issue: 12 (1) Sequence Number: 6053 Start / End Page: - Identifier: ISSN: 2041-1723
CoNE: https://pure.mpg.de/cone/journals/resource/2041-1723