RRC ID 62709
著者 Anuchapreeda S, Rungrojsakul M, Tima S, Chiampanichayakul S, Krig SR.
タイトル Co-activation of WT1 and AP-1 proteins on WT1 gene promoter to induce WT1 gene expression in K562 cells.
ジャーナル Cell Signal
Abstract Earlier studies have revealed one function of the inhibitory mechanism of curcumin. Activating PKCα induces WT1 gene expression via signalling through downstream JNK and c-JUN. In the present study, the effect of c-JUN/AP-1 binding and transcriptional regulation of the WT1 gene promoter was investigated in K562 leukaemic cells. The non-cytotoxic dose (IC20 values) of curcumin (WT1 and AP-1 inhibitors) was employed to examine its effect on WT1 gene-mediated WT1 and AP-1 protein expression. Non-cytotoxic doses of both tanshinone IIA (AP-1 DNA-binding inhibitor) and SP600125 (JNK inhibitor) were used to test the role of c-JUN/AP-1 in WT1 gene expression. Curcumin, tanshinone IIA, and SP600125 inhibited WT1 protein expression in a dose-dependent manner (5-15 μM) at 24 h as shown by immunoblotting. A ChIP assay showed that curcumin and tanshinone IIA inhibited AP-1 and WT1 binding to the proximal WT1 promoter (-301 bp), and a luciferase reporter assay showed that the WT1 luciferase gene reporter activity was decreased after curcumin, tanshinone IIA, and SP600126 treatments. Furthermore, depletion of c-JUN abrogated WT1 gene expression. In summary, AP-1 contributes to the WT1 autoregulation of WT1 gene expression in leukaemic K562 cells.
巻・号 53
ページ 339-347
公開日 2019-1-1
DOI 10.1016/j.cellsig.2018.11.001
PII S0898-6568(18)30271-7
PMID 30395942
MeSH Abietanes / pharmacology Anthracenes / pharmacology Antineoplastic Agents / pharmacology Curcumin / pharmacology Gene Expression Regulation, Leukemic* / drug effects Humans K562 Cells Leukemia / drug therapy Leukemia / genetics* Promoter Regions, Genetic / drug effects Protein Kinase Inhibitors / pharmacology Transcription Factor AP-1 / genetics* WT1 Proteins / genetics*
IF 3.968
リソース情報
ヒト・動物細胞 K562(RCB1897)