Human T-cell Leukemia Virus Type 1 Oncoprotein Tax Represses ZNF268 Expression Through the CAMP-responsive Element-binding Protein/activating Transcription Factor Pathway

Overview

Journal J Biol Chem

Specialty Biochemistry

Date 2008 Apr 1

PMID 18375384

Citations 13

Authors

Di Wang

Ming-Xiong Guo

Hai-Ming Hu

Zhou-Zhou Zhao

Hong-Ling Qiu

Huan-Jie Shao

Chen-Gang Zhu

Lu Xue

Yun-Bo Shi

Wen-Xin Li

Affiliations

Soon will be listed here.

Abstract

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.

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