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J Biol Chem. 2014 Aug 8;289(32):22078-89. doi: 10.1074/jbc.M114.553248. Epub 2014 Jun 24.

Chemical proteomics identifies heterogeneous nuclear ribonucleoprotein (hnRNP) A1 as the molecular target of quercetin in its anti-cancer effects in PC-3 cells.

Author information

1
From the Graduate Institute of Biochemistry and Molecular Biology, College of Medicine, National Taiwan University, Taipei 100, Taiwan and.
2
Eurofins Panlabs Taiwan Ltd., 158 Li-Teh Road, Peitou, Taipei 112, Taiwan.
3
From the Graduate Institute of Biochemistry and Molecular Biology, College of Medicine, National Taiwan University, Taipei 100, Taiwan and chowip@ntu.edu.tw.

Abstract

Quercetin, a flavonoid abundantly present in plants, is widely used as a phytotherapy in prostatitis and prostate cancer. Although quercetin has been reported to have a number of therapeutic effects, the cellular target(s) responsible for its anti-cancer action has not yet been clearly elucidated. Here, employing affinity chromatography and mass spectrometry, we identified heterogeneous nuclear ribonucleoprotein A1 (hnRNPA1) as a direct target of quercetin. A specific interaction between quercetin and hnRNPA1 was validated by immunoblotting and in vitro binding experiments. We found that quercetin bound the C-terminal region of hnRNPA1, impairing the ability of hnRNPA1 to shuttle between the nucleus and cytoplasm and ultimately resulting in its cytoplasmic retention. In addition, hnRNPA1 was recruited to stress granules after treatment of cells with quercetin for up to 48 h, and the levels of cIAP1 (cellular inhibitor of apoptosis), an internal ribosome entry site translation-dependent protein, were reduced by hnRNPA1 regulation. This is the first report that anti-cancer effects of quercetin are mediated, in part, by impairing functions of hnRNPA1, insights that were obtained using a chemical proteomics strategy.

KEYWORDS:

Chemical Proteomics; Molecular Target; Natural Product; Prostate Cancer; Protein Targeting; Proteomics; Quercetin; RNA-binding Protein; hnRNPA1

PMID:
24962584
PMCID:
PMC4139222
DOI:
10.1074/jbc.M114.553248
[Indexed for MEDLINE]
Free PMC Article
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