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Human T-cell leukemia virus type 1 oncoprotein tax represses ZNF268 expression through the cAMP-responsive

Di Wang1, Ming-Xiong Guo, Hai-Ming Hu

  • 1State Key Laboratory of Virology, College of Life Sciences, Wuhan University, Wuhan 430072, China.

The Journal of Biological Chemistry
|April 1, 2008
PubMed

Insights

The human T-cell leukemia virus type 1 (HTLV-1) oncoprotein Tax represses the ZNF268 gene. This repression occurs via the cAMP-responsive element-binding protein (CREB) pathway, impacting T-cell proliferation in HTLV-1 diseases.

Area of Science:

  • Molecular Biology
  • Virology
  • Oncology

Background:

  • Human T-cell leukemia virus type 1 (HTLV-1) oncoprotein Tax drives adult T-cell leukemia.
  • ZNF268 gene is crucial for blood cell differentiation and leukemia pathogenesis.

Purpose of the Study:

  • Investigate the role of HTLV-1 Tax in regulating the ZNF268 gene.
  • Elucidate the molecular mechanisms underlying ZNF268 repression by Tax.

Main Methods:

  • Analysis of ZNF268 mRNA levels in HTLV-1-infected cells.
  • Reporter assays using ZNF268 promoter constructs and mutants.
  • Electrophoretic mobility shift assays and chromatin immunoprecipitation.

Main Results:

  • HTLV-1 Tax expression repressed ZNF268 mRNA and promoter activity.
  • Repression was dependent on a functional cAMP-responsive element.
  • Tax repressed ZNF268 via the CREB/activating transcription factor pathway, forming a Tax.CREB-1 complex.

Conclusions:

  • HTLV-1 Tax directly represses ZNF268 expression through the CREB pathway.
  • ZNF268 may play a role in the aberrant T-cell proliferation seen in HTLV-1-associated diseases.

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