Tumor suppressor death-associated protein kinase 1 inhibits necroptosis by p38 MAPK activation.

Animals Caspase 8 / metabolism Cell Survival Death-Associated Protein Kinases / deficiency Down-Regulation Enzyme Activation Fas-Associated Death Domain Protein / metabolism Gene Knockdown Techniques HT29 Cells Humans Intracellular Signaling Peptides and Proteins / metabolism Mice, Inbred C57BL Mice, Knockout Myeloid Cells / enzymology Necroptosis Phosphorylation Phosphoserine / metabolism Protein Binding Protein Kinases / metabolism Protein Serine-Threonine Kinases / metabolism Receptor-Interacting Protein Serine-Threonine Kinases / metabolism Shock, Septic / metabolism Signal Transduction Tumor Necrosis Factor-alpha p38 Mitogen-Activated Protein Kinases / metabolism

Journal

Cell death & disease
ISSN: 2041-4889
Titre abrégé: Cell Death Dis
Pays: England
ID NLM: 101524092

Informations de publication

Date de publication:
04 05 2020
Historique:
received: 16 12 2019
accepted: 20 04 2020
revised: 17 04 2020
entrez: 6 5 2020
pubmed: 6 5 2020
medline: 23 3 2021
Statut: epublish

Résumé

Death-associated protein kinase 1 (DAPK1, DAPk, DAPK) is known for its involvement in apoptosis and autophagy-associated cell death. Here, we identified an unexpected function of DAPK1 in suppressing necroptosis. DAPK1-deficiency renders macrophages and dendritic cells susceptible to necroptotic death. We also observed an inhibitory role for DAPK1 in necroptosis in HT-29 cells, since knockdown or knockout of DAPK1 in such cells increased their sensitivity to necroptosis. Increased necroptosis was associated with enhanced formation of the RIPK1-RIPK3-MLKL complex in these DAPK1-deficient cells. We further found that DAPK1-deficiency led to decreased MAPK activated kinase 2 (MK2) activation and reduced RIPK1 S321 phosphorylation, with this latter representing a critical step controlling necrosome formation. Most TNF signaling pathways, including ERK, JNK, and AKT, were not regulated by DAPK. In contrast, DAPK bound p38 MAPK and selectively promoted p38 MAPK activation, resulting in enhanced MK2 phosphorylation. Our results reveal a novel role for DAPK1 in inhibiting necroptosis and illustrate an unexpected selectivity for DAPK1 in promoting p38 MAPK-MK2 activation. Importantly, our study suggests that modulation of necroptosis and p38/MK2-mediated inflammation may be achieved by targeting DAPK1.

Identifiants

DOI: 10.1038/s41419-020-2534-9 PMID: 32366830 PMC: PMC7198492
pubmed: 32366830
doi: 10.1038/s41419-020-2534-9
pii: 10.1038/s41419-020-2534-9
pmc: PMC7198492
doi:

Substances chimiques

Fas-Associated Death Domain Protein 0
Intracellular Signaling Peptides and Proteins 0
Tumor Necrosis Factor-alpha 0
Phosphoserine 17885-08-4
MLKL protein, human EC 2.7.-
Protein Kinases EC 2.7.-
MAP-kinase-activated kinase 2 EC 2.7.1.-
DAPK1 protein, human EC 2.7.11.1
Dapk1 protein, mouse EC 2.7.11.1
Death-Associated Protein Kinases EC 2.7.11.1
Protein Serine-Threonine Kinases EC 2.7.11.1
RIPK1 protein, human EC 2.7.11.1
RIPK3 protein, human EC 2.7.11.1
Receptor-Interacting Protein Serine-Threonine Kinases EC 2.7.11.1
p38 Mitogen-Activated Protein Kinases EC 2.7.11.24
Caspase 8 EC 3.4.22.-

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

305

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Auteurs

Yung-Hsuan Wu (YH)

Institute of Molecular Biology, Academia Sinica, Taipei, 11529, Taiwan.

Ting-Fang Chou (TF)

Institute of Molecular Biology, Academia Sinica, Taipei, 11529, Taiwan.

Leslie Young (L)

Institute of Molecular Biology, Academia Sinica, Taipei, 11529, Taiwan.

Fu-Yi Hsieh (FY)

Institute of Molecular Biology, Academia Sinica, Taipei, 11529, Taiwan.

Hsuan-Yin Pan (HY)

Institute of Molecular Biology, Academia Sinica, Taipei, 11529, Taiwan.

Shu-Ting Mo (ST)

Institute of Molecular Biology, Academia Sinica, Taipei, 11529, Taiwan.

Shani Bialik Brown (SB)

Department of Molecular Genetics, Weizmann Institute of Science, Rehovot, 76100, Israel.

Ruey-Hwa Chen (RH)

Institute of Biological Chemistry, Academia Sinica, Taipei, 11529, Taiwan.

Adi Kimchi (A)

Department of Molecular Genetics, Weizmann Institute of Science, Rehovot, 76100, Israel.

Ming-Zong Lai (MZ)

Institute of Molecular Biology, Academia Sinica, Taipei, 11529, Taiwan. mblai@gate.sinica.edu.tw.
ORCID: 0000-0002-3237-4803

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Classifications MeSH

questionsmedicales.fr › Eucaryotes › Animaux › Tumor suppressor death-associated protein...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines et peptides de signalisation intracellulaire › Protéines régulatrices de l'apoptose › Protéines adaptatrices de signalisation des récepteurs à domaine de mort › Caspase 8 › Tumor suppressor death-associated protein...
questionsmedicales.fr › Phénomènes physiologiques cellulaires › Survie cellulaire › Tumor suppressor death-associated protein...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines et peptides de signalisation intracellulaire › Protein-Serine-Threonine Kinases › Calcium-Calmodulin-Dependent Protein Kinases › Death-associated protein kinases › Tumor suppressor death-associated protein...
questionsmedicales.fr › Phénomènes physiologiques › Phénomènes pharmacologiques et toxicologiques › Phénomènes pharmacologiques › Régulation négative › Tumor suppressor death-associated protein...
questionsmedicales.fr › Métabolisme › Activation enzymatique › Tumor suppressor death-associated protein...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines et peptides de signalisation intracellulaire › Protéines régulatrices de l'apoptose › Protéines adaptatrices de signalisation des récepteurs à domaine de mort › Protéine à domaine de mort associée à Fas › Tumor suppressor death-associated protein...
questionsmedicales.fr › Techniques d'investigation › Techniques génétiques › Ciblage de gène › Techniques de knock-down de gènes › Tumor suppressor death-associated protein...
questionsmedicales.fr › Cellules › Cellules épithéliales › Cellules HT29 › Tumor suppressor death-associated protein...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Hominidae › Humains › Tumor suppressor death-associated protein...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines et peptides de signalisation intracellulaire › Tumor suppressor death-associated protein...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Rodentia › Muridae › Murinae › Souris › Lignées consanguines de souris › Souris de lignée C57BL › Tumor suppressor death-associated protein...
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questionsmedicales.fr › Cellules › Cellules myéloïdes › Tumor suppressor death-associated protein...
questionsmedicales.fr › Phénomènes physiologiques cellulaires › Mort cellulaire › Mort cellulaire régulée › Nécroptose › Tumor suppressor death-associated protein...
questionsmedicales.fr › Métabolisme › Phosphorylation › Tumor suppressor death-associated protein...
questionsmedicales.fr › Acides aminés, peptides et protéines › Acides aminés › Acides phosphoaminés › Phosphosérine › Tumor suppressor death-associated protein...
questionsmedicales.fr › Métabolisme › Liaison aux protéines › Tumor suppressor death-associated protein...
questionsmedicales.fr › Enzymes et coenzymes › Enzymes › Transferases › Phosphotransferases › Phosphotransferases (Alcohol Group Acceptor) › Protein kinases › Tumor suppressor death-associated protein...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines et peptides de signalisation intracellulaire › Protein-Serine-Threonine Kinases › Tumor suppressor death-associated protein...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines et peptides de signalisation intracellulaire › Protein-Serine-Threonine Kinases › Receptor-Interacting Protein Serine-Threonine Kinases › Tumor suppressor death-associated protein...
questionsmedicales.fr › États, signes et symptômes pathologiques › Processus pathologiques › Choc › Syndrome de réponse inflammatoire généralisée › Choc septique › Tumor suppressor death-associated protein...
questionsmedicales.fr › Phénomènes physiologiques cellulaires › Transduction du signal › Tumor suppressor death-associated protein...
questionsmedicales.fr › Facteurs biologiques › Protéines et peptides de signalisation intercellulaire › Cytokines › Facteurs de nécrose tumorale › Facteur de nécrose tumorale alpha › Tumor suppressor death-associated protein...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines et peptides de signalisation intracellulaire › Protein-Serine-Threonine Kinases › Mitogen-Activated Protein Kinases › p38 Mitogen-Activated Protein Kinases › Tumor suppressor death-associated protein...