title: Chemical proteomics identifies heterogeneous nuclear ribonucleoprotein (hnRNP) A1 as the molecular target of quercetin in its anti-cancer effects in PC-3 cells.
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.
authors: From the Graduate Institute of Biochemistry and Molecular Biology, College of Medicine, National Taiwan University, Taipei 100, Taiwan and.
authors: Chia-Chen
authors: CC
authors: Ko
authors: From the Graduate Institute of Biochemistry and Molecular Biology, College of Medicine, National Taiwan University, Taipei 100, Taiwan and.
authors: Yun-Ju
authors: YJ
authors: Chen
authors: From the Graduate Institute of Biochemistry and Molecular Biology, College of Medicine, National Taiwan University, Taipei 100, Taiwan and.
authors: Chih-Ta
authors: CT
authors: Chen
authors: From the Graduate Institute of Biochemistry and Molecular Biology, College of Medicine, National Taiwan University, Taipei 100, Taiwan and.
authors: Yu-Chih
authors: YC
authors: Liu
authors: Eurofins Panlabs Taiwan Ltd., 158 Li-Teh Road, Peitou, Taipei 112, Taiwan.
authors: Fong-Chi
authors: FC
authors: Cheng
authors: From the Graduate Institute of Biochemistry and Molecular Biology, College of Medicine, National Taiwan University, Taipei 100, Taiwan and.
authors: Kai-Chao
authors: KC
authors: Hsu
authors: From the Graduate Institute of Biochemistry and Molecular Biology, College of Medicine, National Taiwan University, Taipei 100, Taiwan and chowip@ntu.edu.tw.
authors: Lu-Ping
authors: LP
authors: Chow
mesh_terms: D000595:Amino Acid Sequence; D000972:Antineoplastic Agents, Phytogenic / Q000493:pharmacokinetics / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D001665:Binding Sites; D001693:Biological Transport, Active; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D000076245:Heterogeneous Nuclear Ribonucleoprotein A1; D034481:Heterogeneous-Nuclear Ribonucleoprotein Group A-B / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins / Q000378:metabolism; D008297:Male; D008954:Models, Biological; D008969:Molecular Sequence Data; D050505:Mutant Proteins / Q000235:genetics / Q000378:metabolism; D008517:Phytotherapy; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism*; D011485:Protein Binding; D040901:Proteomics; D011794:Quercetin / Q000493:pharmacokinetics / Q000494:pharmacology*; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D028961:beta Karyopherins / Q000378:metabolism
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D000076245:Heterogeneous Nuclear Ribonucleoprotein A1; D034481:Heterogeneous-Nuclear Ribonucleoprotein Group A-B; D051034:Inhibitor of Apoptosis Proteins; D050505:Mutant Proteins; D011994:Recombinant Proteins; C108121:TNPO1 protein, human; D028961:beta Karyopherins; C000619656:hnRNPA1 protein, human; D011794:Quercetin
keywords: Chemical Proteomics; Molecular Target; Natural Product; Prostate Cancer; Protein Targeting; Proteomics; Quercetin; RNA-binding Protein; hnRNPA1