HTLV-1 bZIP factor supports proliferation of adult T cell leukemia cells through suppression of C/EBPα signaling

Retrovirology
Tiejun ZhaoMasao Matsuoka

Abstract

Human T-cell leukemia virus type 1 (HTLV-1) is an oncogenic retrovirus etiologically associated with adult T-cell leukemia (ATL). The HTLV-1 bZIP factor (HBZ), which is encoded by minus strand of provirus, is expressed in all ATL cases and supports the proliferation of ATL cells. However, the precise mechanism of growth promoting activity of HBZ is poorly understood. In this study, we showed that HBZ suppressed C/EBPα signaling activation induced by either Tax or C/EBPα. As mechanisms of HBZ-mediated C/EBPα inhibition, we found that HBZ physically interacted with C/EBPα and diminished its DNA binding capacity. Luciferase and immunoprecipitation assays revealed that HBZ repressed C/EBPα activation in a Smad3-dependent manner. In addition, C/EBPα was overexpressed in HTLV-1 infected cell lines and fresh ATL cases. HBZ was able to induce C/EBPα transcription by enhancing its promoter activity. Finally, HBZ selectively modulated the expression of C/EBPα target genes, leading to the impairment of C/EBPα-mediated cell growth suppression. HBZ, by suppressing C/EBPα signaling, supports the proliferation of HTLV-1 infected cells, which is thought to be critical for oncogenesis.

References

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Jul 13, 2012·Frontiers in Microbiology·Tiejun Zhao, Masao Matsuoka

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Citations

Feb 6, 2016·Viruses·Tiejun Zhao
Jan 13, 2016·Archiv der Pharmazie·Amr M El-ArabyMoustafa E El-Araby
Mar 17, 2016·Retrovirology·Guangyong MaMasao Matsuoka
Feb 24, 2015·Trends in Microbiology·Benoit Barbeau, Jean-Michel Mesnard
Apr 11, 2017·Acta Pharmacologica Sinica·Lan-Lan ZhangJi-Long Chen
Jan 10, 2020·Retrovirology·Masao Matsuoka, Jean-Michel Mesnard
Mar 9, 2018·Frontiers in Microbiology·Stefania FochiMaria G Romanelli

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Methods Mentioned

BETA
immunoprecipitation assay
confocal microscopy
ChIP
immunoprecipitation
transfection
co-immunoprecipitation assay
PCR
flow cytometry
PMA

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