Human T-cell Leukemia Virus Type 1 Oncoprotein Tax Represses ZNF268 Expression through the cAMP-responsive Element-binding Protein/Activating Transcription Factor Pathway

Expression of the human T-cell leukemia virus type 1 (HTLV-1) oncoprotein Tax is correlated with cellular transformation, contributing to the development of adult T-cell leukemia. In this study, we investigated the role of Tax in the regulation of the ZNF268 gene, which plays a role in the different...

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Veröffentlicht in:The Journal of biological chemistry 2008-06, Vol.283 (24), p.16299-16308
Hauptverfasser: Wang, Di, Guo, Ming-Xiong, Hu, Hai-Ming, Zhao, Zhou-Zhou, Qiu, Hong-Ling, Shao, Huan-Jie, Zhu, Chen-Gang, Xue, Lu, Shi, Yun-Bo, Li, Wen-Xin
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container_end_page 16308
container_issue 24
container_start_page 16299
container_title The Journal of biological chemistry
container_volume 283
creator Wang, Di
Guo, Ming-Xiong
Hu, Hai-Ming
Zhao, Zhou-Zhou
Qiu, Hong-Ling
Shao, Huan-Jie
Zhu, Chen-Gang
Xue, Lu
Shi, Yun-Bo
Li, Wen-Xin
description Expression of the human T-cell leukemia virus type 1 (HTLV-1) oncoprotein Tax is correlated with cellular transformation, contributing to the development of adult T-cell leukemia. In this study, we investigated the role of Tax in the regulation of the ZNF268 gene, which plays a role in the differentiation of blood cells and the pathogenesis of leukemia. We demonstrated that ZNF268 mRNA was repressed in HTLV-1-infected cells. We also showed that stable and transient expression of HTLV-1 Tax led to repression of ZNF268. In addition, by using reporter constructs that bear the human ZNF268 promoter and its mutants, we showed that Tax repressed ZNF268 promoter in a process dependent on a functional cAMP-responsive element. By using Tax, cAMP-responsive element-binding protein (CREB)-1, CREB-2, and their mutants, we further showed that Tax repressed ZNF268 through the CREB/activating transcription factor pathway. Electrophoretic mobility shift assays and chromatin immunoprecipitation demonstrated the formation of the complex of Tax·CREB-1 directly at the cAMP-responsive element both in vitro and in vivo. These findings suggest a role for ZNF268 in aberrant T-cell proliferation observed in HTLV-1-associated diseases.
doi_str_mv 10.1074/jbc.M706426200
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In this study, we investigated the role of Tax in the regulation of the ZNF268 gene, which plays a role in the differentiation of blood cells and the pathogenesis of leukemia. We demonstrated that ZNF268 mRNA was repressed in HTLV-1-infected cells. We also showed that stable and transient expression of HTLV-1 Tax led to repression of ZNF268. In addition, by using reporter constructs that bear the human ZNF268 promoter and its mutants, we showed that Tax repressed ZNF268 promoter in a process dependent on a functional cAMP-responsive element. By using Tax, cAMP-responsive element-binding protein (CREB)-1, CREB-2, and their mutants, we further showed that Tax repressed ZNF268 through the CREB/activating transcription factor pathway. Electrophoretic mobility shift assays and chromatin immunoprecipitation demonstrated the formation of the complex of Tax·CREB-1 directly at the cAMP-responsive element both in vitro and in vivo. 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subjects Activating Transcription Factor 1 - metabolism
Base Sequence
Cyclic AMP - metabolism
Cyclic AMP Response Element-Binding Protein - metabolism
DNA-Binding Proteins - metabolism
Gene Expression Regulation
Gene Products, tax - physiology
Human T-lymphotropic virus 1
Human T-lymphotropic virus 1 - metabolism
Humans
Mechanisms of Signal Transduction
Models, Biological
Models, Genetic
Molecular Sequence Data
Mutation
Promoter Regions, Genetic
Protein Binding
Repressor Proteins - metabolism
title Human T-cell Leukemia Virus Type 1 Oncoprotein Tax Represses ZNF268 Expression through the cAMP-responsive Element-binding Protein/Activating Transcription Factor Pathway
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