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@ARTICLE{Chauhan:277799,
author = {C. Chauhan and A. Kraemer$^*$ and S. Knapp$^*$ and M.
Windheim and A. Kotlyarov and M. B. Menon and M. Gaestel},
title = {5-{I}odotubercidin sensitizes cells to {RIPK}1-dependent
necroptosis by interfering with {NF}κ{B} signaling.},
journal = {Cell death discovery},
volume = {9},
number = {1},
issn = {2058-7716},
address = {London},
publisher = {Nature Publishing Group},
reportid = {DKFZ-2023-01510},
pages = {262},
year = {2023},
abstract = {Receptor-interacting protein kinases (RIPK)-1 and -3 play
crucial roles in cell fate decisions and are regulated by
multiple checkpoint controls. Previous studies have
identified IKK1/2- and p38/MK2-dependent checkpoints that
phosphorylate RIPK1 at different residues to inhibit its
activation. In this study, we investigated TNF-induced death
in MAPK-activated protein kinase 2 (MK2)-deficient cells and
found that MK2 deficiency or inactivation predominantly
leads to necroptotic cell death, even without caspase
inhibition. While RIPK1 inhibitors can rescue MK2-deficient
cells from necroptosis, inhibiting RIPK3 seems to switch the
process to apoptosis. To understand the underlying mechanism
of this switch, we screened a library of 149 kinase
inhibitors and identified the adenosine analog
5-Iodotubercidin (5-ITu) as the most potent compound that
sensitizes MK2-deficient MEFs to TNF-induced cell death.
5-ITu also enhances LPS-induced necroptosis when combined
with MK2 inhibition in RAW264.7 macrophages. Further
mechanistic studies revealed that 5-ITu induces
RIPK1-dependent necroptosis by suppressing IKK signaling in
the absence of MK2 activity. These findings highlight the
role for the multitarget kinase inhibitor 5-ITu in TNF-,
LPS- and chemotherapeutics-induced necroptosis and its
potential implications in RIPK1-targeted therapies.},
cin = {FM01},
ddc = {610},
cid = {I:(DE-He78)FM01-20160331},
pnm = {899 - ohne Topic (POF4-899)},
pid = {G:(DE-HGF)POF4-899},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:37495567},
doi = {10.1038/s41420-023-01576-x},
url = {https://inrepo02.dkfz.de/record/277799},
}