title: Identification of novel signaling components in genistein-regulated signaling pathways by quantitative phosphoproteomics.
abstract: Isolated from soybeans, genistein is an isoflavonoid that exhibits anti-carcinogenic effects. Genistein could induce G2/M arrest and apoptosis of various cancer cells in vivo and in vitro. Although ERK1/2, AKT, p90RSK and NFκB were previously found to be regulated by genistein, most of signaling components in genistein-inhibited signaling pathways were still unknown. Here, we used SILAC quantitative phosphoproteomics to globally identify the phosphoproteins and their regulatory sites in signaling pathways mediated by genistein. We detected 1177 phosphorylation sites on 635 unique proteins; among them, 320 phosphorylation sites on 222 unique phosphopeptides representing 215 non-redundant proteins were modulated at least 1.5-folds by genistein. Apart from ERK1/2, PI3K, p90RSK, Bad and topoisomerase that are known genistein-regulated effectors, many novel phosphoproteins were identified for the first time to be involved in genistein-regulated signal transduction networks. They mainly include 9 receptors, 5 signal adaptors, 13 protein kinases, 2 protein phosphatase regulatory subunits, and 14 transcription regulators. Several of these phosphoproteins have been proven to be involved in G2/M arrest or apoptosis such as GPCRs, DCC, NCK1, TNK2, BTK, TP53BP1, BCLAF, MAX and MAG. This dataset provides valuable insights into the cancer-related phosphorylation signaling pathways regulated by genistein.
authors.affiliation: Institute of Life and Health Engineering, and National Engineering and Research Center for Genetic Medicine, Jinan University, Guangzhou 510632, China. tgryan@jnu.edu.cn
authors.forename: Guang-Rong
authors.initials: GR
authors.lastname: Yan
authors.forename: Xing-Feng
authors.initials: XF
authors.lastname: Yin
authors.forename: Chuan-Le
authors.initials: CL
authors.lastname: Xiao
authors.forename: Zi-Lu
authors.initials: ZL
authors.lastname: Tan
authors.forename: Song-Hui
authors.initials: SH
authors.lastname: Xu
authors.forename: Qing-Yu
authors.initials: QY
authors.lastname: He
mesh_terms: D045744:Cell Line, Tumor; D019833:Genistein / Q000494:pharmacology*; D006801:Humans; D007553:Isotope Labeling / Q000379:methods; D010748:Phosphopeptides / Q000378:metabolism; D010750:Phosphoproteins / Q000378:metabolism; D010766:Phosphorylation; D040901:Proteomics / Q000379:methods*; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*
chemical_list: D010748:Phosphopeptides; D010750:Phosphoproteins; D019833:Genistein