The Oncogenic Action of NRF2 Depends on De-glycation by Fructosamine-3-Kinase.

Détails

ID Serval
serval:BIB_C338CC40D7D4
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
The Oncogenic Action of NRF2 Depends on De-glycation by Fructosamine-3-Kinase.
Périodique
Cell
Auteur(s)
Sanghvi V.R., Leibold J., Mina M., Mohan P., Berishaj M., Li Z., Miele M.M., Lailler N., Zhao C., de Stanchina E., Viale A., Akkari L., Lowe S.W., Ciriello G., Hendrickson R.C., Wendel H.G.
ISSN
1097-4172 (Electronic)
ISSN-L
0092-8674
Statut éditorial
Publié
Date de publication
08/08/2019
Peer-reviewed
Oui
Volume
178
Numéro
4
Pages
807-819.e21
Langue
anglais
Notes
Publication types: Journal Article
Publication Status: ppublish
Résumé
The NRF2 transcription factor controls a cell stress program that is implicated in cancer and there is great interest in targeting NRF2 for therapy. We show that NRF2 activity depends on Fructosamine-3-kinase (FN3K)-a kinase that triggers protein de-glycation. In its absence, NRF2 is extensively glycated, unstable, and defective at binding to small MAF proteins and transcriptional activation. Moreover, the development of hepatocellular carcinoma triggered by MYC and Keap1 inactivation depends on FN3K in vivo. N-acetyl cysteine treatment partially rescues the effects of FN3K loss on NRF2 driven tumor phenotypes indicating a key role for NRF2-mediated redox balance. Mass spectrometry reveals that other proteins undergo FN3K-sensitive glycation, including translation factors, heat shock proteins, and histones. How glycation affects their functions remains to be defined. In summary, our study reveals a surprising role for the glycation of cellular proteins and implicates FN3K as targetable modulator of NRF2 activity in cancer.
Mots-clé
EGFR, FN3K, KEAP1, NRF2, de-glycation, fructosamine, glucose, glycation, hepatocellular carcinoma, redox
Pubmed
Création de la notice
16/08/2019 20:04
Dernière modification de la notice
21/08/2019 5:34
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