title: Tax is involved in up-regulation of HMGB1 expression levels by interaction with C/EBP.
abstract: The high mobility group box 1 (HMGB1) protein is a multifunctional cytokine-like molecule that plays an important role in the pathogenesis of tumors. In this study, real-time polymerase chain reactions and Western blot assays indicated that HMGB1 transcriptional activity and protein level are increased in Tax+-T cells (TaxP). To clarify the mechanisms, a series of HMGB1 deletion reporter plasmids (pHLuc1 to pHLuc6) were transfected into Tax--T cells (TaxN, Jurkat) and Tax+-T cells (TaxP). We found that promoter activity in Tax+-T cells to be higher than that in Tax--T cells, indicating a significant increase in pHLuc6. Bay11-7082 (NF-κB inhibitor) treatment did not block the enhancing effect. Chromatin immunoprecipitation assays revealed that Tax was retained on a HMGB1 promoter fragment encompassing -1163 to -975. Bioinformatics analysis showed six characteristic cis-elements for CdxA, AP-1, AML-1a, USF, v-Myb, and C/EBP in the fragment in question. Mutation of cis- elements for C/EBP reduced significant HMGB1 promoter activity induced by Tax. These findings indicate that Tax enhances the expression of HMGB1 gene at the transcriptional level, possibly by interacting with C/EBP.
authors.affiliation: Clinical Laboratory Medicine Department, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China.
authors.forename: Chen-Guang
authors.initials: CG
authors.lastname: Zhang
authors.forename: Hui
authors.initials: H
authors.lastname: Wang
authors.forename: Zhi-Guo
authors.initials: ZG
authors.lastname: Niu
authors.forename: Jing-Jing
authors.initials: JJ
authors.lastname: Zhang
authors.forename: Ming-Mei
authors.initials: MM
authors.lastname: Yin
authors.forename: Zhi-Tao
authors.initials: ZT
authors.lastname: Gao
authors.forename: Li-Hua
authors.initials: LH
authors.lastname: Hu
mesh_terms: D022762:CCAAT-Enhancer-Binding Proteins / Q000378:metabolism*; D015973:Gene Expression Regulation, Leukemic; D016356:Gene Products, tax / Q000235:genetics / Q000378:metabolism*; D017930:Genes, Reporter; D024243:HMGB1 Protein / Q000235:genetics* / Q000378:metabolism*; D006801:Humans; D019169:Jurkat Cells; D015459:Leukemia-Lymphoma, Adult T-Cell / Q000235:genetics*; D016328:NF-kappa B / Q000037:antagonists & inhibitors; D009570:Nitriles / Q000494:pharmacology; D011401:Promoter Regions, Genetic; D013450:Sulfones / Q000494:pharmacology; D013601:T-Lymphocytes / Q000378:metabolism; D014162:Transfection; D015854:Up-Regulation / Q000187:drug effects; D051720:Upstream Stimulatory Factors / Q000378:metabolism
chemical_list: C434003:3-(4-methylphenylsulfonyl)-2-propenenitrile; D022762:CCAAT-Enhancer-Binding Proteins; D016356:Gene Products, tax; D024243:HMGB1 Protein; D016328:NF-kappa B; D009570:Nitriles; D013450:Sulfones; D051720:Upstream Stimulatory Factors; C514970:tax protein, Human T-lymphotrophic virus 1