English
 
Help Privacy Policy Disclaimer
  Advanced SearchBrowse

Item

ITEM ACTIONSEXPORT

Released

Journal Article

Phosphoproteome profiling uncovers a key role for CDKs in TNF signaling

MPS-Authors
/persons/resource/persons227202

Tanzer,  Maria C.
Mann, Matthias / Proteomics and Signal Transduction, Max Planck Institute of Biochemistry, Max Planck Society;

/persons/resource/persons247346

Bludau,  Isabell
Mann, Matthias / Proteomics and Signal Transduction, Max Planck Institute of Biochemistry, Max Planck Society;

/persons/resource/persons78356

Mann,  Matthias
Mann, Matthias / Proteomics and Signal Transduction, Max Planck Institute of Biochemistry, Max Planck Society;

External Resource
Fulltext (restricted access)
There are currently no full texts shared for your IP range.
Fulltext (public)

s41467-021-26289-6.pdf
(Publisher version), 11MB

Supplementary Material (public)
There is no public supplementary material available
Citation

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.


Cite as: https://hdl.handle.net/21.11116/0000-0009-7574-1
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 .