title: NANOG upregulates c-Jun oncogene expression through binding the c-Jun promoter.
abstract: NANOG plays important roles in neoplastic processes. However, the molecular mechanism of NANOG in tumorigenesis remains to be elucidated. In this report, we demonstrated that forced expression of NANOG in 293 cells and cancer cells led to increased c-Jun expression, whereas downregulation of endogenous NANOG significantly reduced c-Jun expression in cancer cells. Dual luciferase reporter assays demonstrated that NANOG binds the c-Jun proximal promoter and transactivates the c-Jun gene. An ATTA consensus motif between the -160 and -268 region of the c-Jun promoter was identified as the NANOG-responsive element. Electromobility shift assay and chromatin immunoprecipitation results confirmed the direct binding of NANOG protein to the c-Jun promoter in vitro and in vivo. NANOG directly bound c-Jun protein as shown by GST pulldown and immunoprecipitation assays. Taking these findings together, we conclude that c-Jun is a direct target gene of NANOG and that c-Jun protein may be a novel co-activator of NANOG in cancer cells. We suggest the possibility that NANOG may play a significant role in carcinogenesis via its activation of c-Jun expression.
authors.affiliation: Laboratory of Cell Engineering, Beijing Institute of Biotechnology, Beijing, P.R. China.
authors.forename: Yanli
authors.initials: Y
authors.lastname: Lin
authors.affiliation: Laboratory of Cell Engineering, Beijing Institute of Biotechnology, Beijing, P.R. China.
authors.forename: Fuyin
authors.initials: F
authors.lastname: Xiong
authors.affiliation: Laboratory of Cell Engineering, Beijing Institute of Biotechnology, Beijing, P.R. China.
authors.forename: Yanrong
authors.initials: Y
authors.lastname: Zhou
authors.affiliation: Laboratory of Cell Engineering, Beijing Institute of Biotechnology, Beijing, P.R. China.
authors.forename: Xiaojie
authors.initials: X
authors.lastname: Wu
authors.affiliation: Laboratory of Cell Engineering, Beijing Institute of Biotechnology, Beijing, P.R. China.
authors.forename: Fang
authors.initials: F
authors.lastname: Liu
authors.affiliation: Laboratory of Cell Engineering, Beijing Institute of Biotechnology, Beijing, P.R. China.
authors.forename: Shiwei
authors.initials: S
authors.lastname: Xue
authors.affiliation: Laboratory of Cell Engineering, Beijing Institute of Biotechnology, Beijing, P.R. China.
authors.forename: Hongxing
authors.initials: H
authors.lastname: Chen
mesh_terms: D001665:Binding Sites / Q000235:genetics; D002460:Cell Line; D045744:Cell Line, Tumor; D002471:Cell Transformation, Neoplastic / Q000235:genetics; D047369:Chromatin Immunoprecipitation / Q000379:methods; D015536:Down-Regulation / Q000235:genetics; D005801:Genes, Homeobox / Q000235:genetics; D057809:HEK293 Cells; D006367:HeLa Cells; D056945:Hep G2 Cells; D018398:Homeodomain Proteins / Q000235:genetics*; D006801:Humans; D000071317:Nanog Homeobox Protein; D011401:Promoter Regions, Genetic / Q000235:genetics; D011485:Protein Binding / Q000235:genetics*; D016755:Proto-Oncogene Proteins c-jun / Q000235:genetics*; D015533:Transcriptional Activation / Q000235:genetics; D015854:Up-Regulation / Q000235:genetics*
chemical_list: D018398:Homeodomain Proteins; C486780:NANOG protein, human; D000071317:Nanog Homeobox Protein; D016755:Proto-Oncogene Proteins c-jun
keywords: NANOG; c-jun; carcinogenesis; transcriptional regulation