title: Transcription of promoter from the human APRIL gene regulated by Sp1 and NF-kB.
abstract: A proliferation-inducing ligand (APRIL) which stimulates the cell proliferation is abundantly expressed in colorectal cancer (CRC) tumors. In this report, the promoter region of the APRIL gene was determined and the major transcription factor was investigated for the first time. Deletion analysis of 5'-ﬂanking region of the human APRIL gene and transient transfection revealed that a 538 bp region (from -1539 to -1001) was essential for promoter activation of the APRIL gene. The data from electrophoretic mobility shift assays (EMSA) indicated that the 538 bp promoter region was responsive to the specificity protein 1 (Sp1) and nuclear factor kappa B (NF-kB). Overexpression of Sp1 or NF-kB increased the activity of the APRIL promoter. Mithramycin A (inhibitor of Sp1) and Bay11-7082 (inhibitor of NF-kB) exhibited an inhibitory activity to APRIL promoter. Our results will benefit to the APRIL gene regulation investigation and contribute to discover new drug target for the APRIL gene therapy of CRC.
authors.affiliation: Department of Clinical Laboratory Center, Affiliated Hospital of Nantong University, Nantong, China.
authors.forename: J
authors.initials: J
authors.lastname: Xu
authors.forename: W F
authors.initials: WF
authors.lastname: Ding
authors.forename: K K
authors.initials: KK
authors.lastname: Shao
authors.forename: X D
authors.initials: XD
authors.lastname: Wang
authors.forename: G H
authors.initials: GH
authors.lastname: Wang
authors.forename: H Q
authors.initials: HQ
authors.lastname: Li
authors.forename: H M
authors.initials: HM
authors.lastname: Wang
mesh_terms: D001483:Base Sequence; D001665:Binding Sites; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000378:metabolism; D024202:Electrophoretic Mobility Shift Assay; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008156:Luciferases / Q000378:metabolism; D008969:Molecular Sequence Data; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D009570:Nitriles / Q000494:pharmacology; D008926:Plicamycin / Q000031:analogs & derivatives / Q000494:pharmacology; D011401:Promoter Regions, Genetic / Q000235:genetics*; D011485:Protein Binding; D020218:Response Elements; D017384:Sequence Deletion; D016329:Sp1 Transcription Factor / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D013450:Sulfones / Q000494:pharmacology; D014158:Transcription, Genetic; D014407:Tumor Cells, Cultured; D053300:Tumor Necrosis Factor Ligand Superfamily Member 13 / Q000235:genetics* / Q000378:metabolism
chemical_list: C434003:3-(4-methylphenylsulfonyl)-2-propenenitrile; D016328:NF-kappa B; D009570:Nitriles; D016329:Sp1 Transcription Factor; D013450:Sulfones; C114631:TNFSF13 protein, human; D053300:Tumor Necrosis Factor Ligand Superfamily Member 13; C066851:mithramycin A; D008156:Luciferases; D008926:Plicamycin