Gain-of-function mutations in the catalytic domain of
Journal
Science advances
ISSN: 2375-2548
Titre abrégé: Sci Adv
Pays: United States
ID NLM: 101653440
Informations de publication
Date de publication:
02 06 2023
02 06 2023
Historique:
medline:
2
6
2023
pubmed:
31
5
2023
entrez:
31
5
2023
Statut:
ppublish
Résumé
Lung cancer is a lethal malignancy lacking effective therapies. Emerging evidence suggests that epigenetic enzyme mutations are closely related to the malignant phenotype of lung cancer. Here, we identified a series of gain-of-function mutations in the histone methyltransferase DOT1L. The strongest of them is R231Q, located in the catalytic DOT domain. R231Q can enhance the substrate binding ability of DOT1L. Moreover, R231Q promotes cell growth and drug resistance of lung cancer cells in vitro and in vivo. Mechanistic studies also revealed that the R231Q mutant specifically activates the MAPK/ERK signaling pathway by enriching H3K79me2 on the
Identifiants
pubmed: 37256945
doi: 10.1126/sciadv.adc9273
pmc: PMC10413674
doi:
Substances chimiques
DOT1L protein, human
EC 2.1.1.-
Histone-Lysine N-Methyltransferase
EC 2.1.1.43
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
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