Phosphoproteome profiling uncovers a key role for CDKs in TNF signaling

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Standard

Phosphoproteome profiling uncovers a key role for CDKs in TNF signaling. / Tanzer, Maria C; Bludau, Isabell; Stafford, Che A; Hornung, Veit; Mann, Matthias.

In: Nature Communications, Vol. 12, No. 1, 18.10.2021, p. 6053.

Research output: Contribution to journal › Journal article › Research › peer-review

Harvard

Tanzer, MC, Bludau, I, Stafford, CA, Hornung, V & Mann, M 2021, 'Phosphoproteome profiling uncovers a key role for CDKs in TNF signaling', Nature Communications, vol. 12, no. 1, pp. 6053. https://doi.org/10.1038/s41467-021-26289-6

APA

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. https://doi.org/10.1038/s41467-021-26289-6

Vancouver

Tanzer MC, Bludau I, Stafford CA, Hornung V, Mann M. Phosphoproteome profiling uncovers a key role for CDKs in TNF signaling. Nature Communications. 2021 Oct 18;12(1):6053. https://doi.org/10.1038/s41467-021-26289-6

Author

Tanzer, Maria C ; Bludau, Isabell ; Stafford, Che A ; Hornung, Veit ; Mann, Matthias. / Phosphoproteome profiling uncovers a key role for CDKs in TNF signaling. In: Nature Communications. 2021 ; Vol. 12, No. 1. pp. 6053.

Bibtex

@article{c62fc63947b040c6ae2b7b8ad6db7e1d,
title = "Phosphoproteome profiling uncovers a key role for CDKs in TNF signaling",
abstract = "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 http://tnfviewer.biochem.mpg.de/ .",
keywords = "A549 Cells, Apoptosis, Cell Death, Cell Line, Cyclin-Dependent Kinases/metabolism, Cytokines/metabolism, Humans, Necroptosis, Phosphorylation, Proteome/metabolism, Signal Transduction, Tumor Necrosis Factor-alpha/metabolism, U937 Cells",
author = "Tanzer, {Maria C} and Isabell Bludau and Stafford, {Che A} and Veit Hornung and Matthias Mann",
note = "{\textcopyright} 2021. The Author(s).",
year = "2021",
month = oct,
day = "18",
doi = "10.1038/s41467-021-26289-6",
language = "English",
volume = "12",
pages = "6053",
journal = "Nature Communications",
issn = "2041-1723",
publisher = "nature publishing group",
number = "1",

}

RIS

TY - JOUR

T1 - Phosphoproteome profiling uncovers a key role for CDKs in TNF signaling

AU - Tanzer, Maria C

AU - Bludau, Isabell

AU - Stafford, Che A

AU - Hornung, Veit

AU - Mann, Matthias

N1 - © 2021. The Author(s).

PY - 2021/10/18

Y1 - 2021/10/18

N2 - 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 http://tnfviewer.biochem.mpg.de/ .

AB - 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 http://tnfviewer.biochem.mpg.de/ .

KW - A549 Cells

KW - Apoptosis

KW - Cell Death

KW - Cell Line

KW - Cyclin-Dependent Kinases/metabolism

KW - Cytokines/metabolism

KW - Humans

KW - Necroptosis

KW - Phosphorylation

KW - Proteome/metabolism

KW - Signal Transduction

KW - Tumor Necrosis Factor-alpha/metabolism

KW - U937 Cells

U2 - 10.1038/s41467-021-26289-6

DO - 10.1038/s41467-021-26289-6

M3 - Journal article

C2 - 34663829

VL - 12

SP - 6053

JO - Nature Communications

JF - Nature Communications

SN - 2041-1723

IS - 1

ER -

ID: 303115072