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

Zhao, Tiejun, Coutts, Aaron, Xu, Lingling, Yu, Juntao, Ohshima, Koichi and Matsuoka, Masao (2013) HTLV-1 bZIP factor supports proliferation of adult T cell leukemia cells through suppression of C/EBPα signaling. Retrovirology, 10 1: 159.1-159.13. doi:10.1186/1742-4690-10-159


Author Zhao, Tiejun
Coutts, Aaron
Xu, Lingling
Yu, Juntao
Ohshima, Koichi
Matsuoka, Masao
Title HTLV-1 bZIP factor supports proliferation of adult T cell leukemia cells through suppression of C/EBPα signaling
Journal name Retrovirology   Check publisher's open access policy
ISSN 1742-4690
Publication date 2013-12-21
Sub-type Article (original research)
DOI 10.1186/1742-4690-10-159
Open Access Status DOI
Volume 10
Issue 1
Start page 159.1
End page 159.13
Total pages 13
Place of publication London, United Kingdom
Publisher BioMed Central
Subject 2406 Virology
2725 Infectious Diseases
Abstract Background: 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.Results: 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.Conclusion: HBZ, by suppressing C/EBPα signaling, supports the proliferation of HTLV-1 infected cells, which is thought to be critical for oncogenesis.
Keyword C/EBPα
HBZ
HTLV-1
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2014 Collection
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