Tax is Involved in Up-regulation of HMGB1 Expression Levels by Interaction with C/EBP

  • Zhang, Chen-Guang (Clinical Laboratory Medicine Department, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology) ;
  • Wang, Hui (Research Center for Immunology, Department of Laboratory Medicine, Xinxiang Medical University) ;
  • Niu, Zhi-Guo (Research Center for Immunology, Department of Laboratory Medicine, Xinxiang Medical University) ;
  • Zhang, Jing-Jing (Research Center for Immunology, Department of Laboratory Medicine, Xinxiang Medical University) ;
  • Yin, Ming-Mei (Research Center for Immunology, Department of Laboratory Medicine, Xinxiang Medical University) ;
  • Gao, Zhi-Tao (Research Center for Immunology, Department of Laboratory Medicine, Xinxiang Medical University) ;
  • Hu, Li-Hua (Clinical Laboratory Medicine Department, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology)
  • Published : 2013.01.31


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-${\kappa}B$ 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.


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