HTLV-1 bZIP factor supports proliferation of adult T cell leukemia cells through suppression of C-EBPα signalingReport as inadecuate




HTLV-1 bZIP factor supports proliferation of adult T cell leukemia cells through suppression of C-EBPα signaling - Download this document for free, or read online. Document in PDF available to download.

Retrovirology

, 10:159

First Online: 21 December 2013Received: 27 July 2013Accepted: 11 December 2013

Abstract

BackgroundHuman 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.

ResultsIn 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.

ConclusionHBZ, by suppressing C-EBPα signaling, supports the proliferation of HTLV-1 infected cells, which is thought to be critical for oncogenesis.

KeywordsHTLV-1 HBZ C-EBPα Electronic supplementary materialThe online version of this article doi:10.1186-1742-4690-10-159 contains supplementary material, which is available to authorized users.

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Author: Tiejun Zhao - Aaron Coutts - Lingling Xu - Juntao Yu - Koichi Ohshima - Masao Matsuoka

Source: https://link.springer.com/



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