PXD014334 is an
original dataset announced via ProteomeXchange.
Dataset Summary
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 |
Dataset History
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. |
Publication List
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] |
Keyword List
submitter keyword: NRF2, hepatocellular carcinoma (HCC), glycation, FN3K, AGE |
Contact List
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 | |
Full Dataset Link List
Dataset FTP location
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PRIDE project URI |
Repository Record List
[ + ]
[ - ]
- PRIDE
- PXD014334
- Label: PRIDE project
- Name: The oncogenic action of NRF2 depends on de-glycation by Fructosamine-3-kinase (FN3K)