Protein arginine methyltransferase 2 controls inflammatory signaling in acute myeloid leukemia.
Protein-Arginine N-Methyltransferases
/ metabolism
Leukemia, Myeloid, Acute
/ genetics
Animals
Humans
Signal Transduction
Mice
Inflammation
/ metabolism
Mice, Knockout
NF-kappa B
/ metabolism
Cell Line, Tumor
STAT3 Transcription Factor
/ metabolism
Female
Male
Mice, Inbred C57BL
Intracellular Signaling Peptides and Proteins
Journal
Communications biology
ISSN: 2399-3642
Titre abrégé: Commun Biol
Pays: England
ID NLM: 101719179
Informations de publication
Date de publication:
20 Jun 2024
20 Jun 2024
Historique:
received:
19
01
2024
accepted:
14
06
2024
medline:
21
6
2024
pubmed:
21
6
2024
entrez:
20
6
2024
Statut:
epublish
Résumé
Arginine methylation is catalyzed by protein arginine methyltransferases (PRMTs) and is involved in various cellular processes, including cancer development. PRMT2 expression is increased in several cancer types although its role in acute myeloid leukemia (AML) remains unknown. Here, we investigate the role of PRMT2 in a cohort of patients with AML, PRMT2 knockout AML cell lines as well as a Prmt2 knockout mouse model. In patients, low PRMT2 expressors are enriched for inflammatory signatures, including the NF-κB pathway, and show inferior survival. In keeping with a role for PRMT2 in control of inflammatory signaling, bone marrow-derived macrophages from Prmt2 KO mice display increased pro-inflammatory cytokine signaling upon LPS treatment. In PRMT2-depleted AML cell lines, aberrant inflammatory signaling has been linked to overproduction of IL6, resulting from a deregulation of the NF-κB signaling pathway, therefore leading to hyperactivation of STAT3. Together, these findings identify PRMT2 as a key regulator of inflammation in AML.
Identifiants
pubmed: 38902349
doi: 10.1038/s42003-024-06453-6
pii: 10.1038/s42003-024-06453-6
doi:
Substances chimiques
Protein-Arginine N-Methyltransferases
EC 2.1.1.319
NF-kappa B
0
PRMT2 protein, human
EC 2.1.1.319
STAT3 Transcription Factor
0
Intracellular Signaling Peptides and Proteins
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
753Informations de copyright
© 2024. The Author(s).
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