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Tax is involved in up-regulation of HMGB1 expression levels by interaction with C/EBP
- Source :
- Asian Pacific journal of cancer prevention : APJCP. 14(1)
- Publication Year :
- 2013
-
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 ciselements 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.
- Subjects :
- Cancer Research
Epidemiology
T-Lymphocytes
chemical and pharmacologic phenomena
Biology
medicine.disease_cause
Transfection
Jurkat cells
Jurkat Cells
Genes, Reporter
Nitriles
medicine
Transcriptional regulation
Humans
Leukemia-Lymphoma, Adult T-Cell
Sulfones
HMGB1 Protein
Promoter Regions, Genetic
Gene
Regulation of gene expression
Mutation
Gene Expression Regulation, Leukemic
Public Health, Environmental and Occupational Health
NF-kappa B
Gene Products, tax
Molecular biology
Up-Regulation
High-mobility group
Oncology
CCAAT-Enhancer-Binding Proteins
Upstream Stimulatory Factors
Chromatin immunoprecipitation
Subjects
Details
- ISSN :
- 2476762X
- Volume :
- 14
- Issue :
- 1
- Database :
- OpenAIRE
- Journal :
- Asian Pacific journal of cancer prevention : APJCP
- Accession number :
- edsair.doi.dedup.....bc52e86a3f6e0091c5f7ae546b2466ce