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http://dx.doi.org/10.7314/APJCP.2013.14.1.359

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)
Publication Information
Asian Pacific Journal of Cancer Prevention / v.14, no.1, 2013 , pp. 359-365 More about this Journal
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-${\kappa}B$ 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.
Keywords
Human HMGB1 promoter; Tax; transcriptional regulation; C/EBP;
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