PXD014334

PXD014334 is an original dataset announced via ProteomeXchange.

Title	The oncogenic action of NRF2 depends on de-glycation by Fructosamine-3-kinase (FN3K)
Description	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.
HostingRepository	PRIDE
AnnounceDate	2019-07-08
AnnouncementXML	Submission_2019-08-16_00:24:22.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Zhuoning Li
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090; scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	acetylated residue; monohydroxylated residue; iodoacetic acid derivatized residue; iodoacetamide derivatized residue; deamidated residue
Instrument	Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2019-06-21 01:38:30	ID requested
1	2019-07-08 01:08:09	announced
⏵ 2	2019-08-16 00:24:24	announced	Updated publication reference for PubMed record(s): 31398338.

Sanghvi VR, Leibold J, Mina M, Mohan P, Berishaj M, Li Z, Miele MM, Lailler N, Zhao C, de Stanchina E, Viale A, Akkari L, Lowe SW, Ciriello G, Hendrickson RC, Wendel HG, The Oncogenic Action of NRF2 Depends on De-glycation by Fructosamine-3-Kinase. Cell, 178(4):807-819.e21(2019) [pubmed]

submitter keyword: NRF2, hepatocellular carcinoma (HCC), glycation, FN3K, AGE

Hans-Guido Wendel
contact affiliation	Cancer Biology and Genetics Program, Memorial Sloan Kettering Cancer Center, New York
contact email	wendelh@mskcc.org
lab head
Zhuoning Li
contact affiliation	MSKCC
contact email	liz2@mskcc.org
dataset submitter

Dataset FTP location NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2019/07/PXD014334

PRIDE project URI

• PRIDE
  1. PXD014334
     1. Label: PRIDE project
     2. Name: The oncogenic action of NRF2 depends on de-glycation by Fructosamine-3-kinase (FN3K)