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

Zhao, T; Coutts, A; Xu, L; Yu, J; Ohshima, K; Matsuoka, M

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

Zhao, T Coutts, A Xu, L Yu, J Ohshima, K Matsuoka, M

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Publisher:: BioMed Central
Publication Type:: Journal Article
Citation:: Retrovirology, 2013, 10 pp. 1 - 13
Issue Date:: 2013-12-21

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Field	Value	Language
dc.contributor.author	Zhao, T	en_US
dc.contributor.author	Coutts, A	en_US
dc.contributor.author	Xu, L	en_US
dc.contributor.author	Yu, J	en_US
dc.contributor.author	Ohshima, K	en_US
dc.contributor.author	Matsuoka, M	en_US
dc.date.accessioned	2017-09-18T05:57:30Z
dc.date.available	2013-12-11	en_US
dc.date.available	2017-09-18T05:57:30Z
dc.date.issued	2013-12-21	en_US
dc.identifier.citation	Retrovirology, 2013, 10 pp. 1 - 13	en_US
dc.identifier.issn	1742-4690	en_US
dc.identifier.uri	http://hdl.handle.net/10453/117262
dc.description.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.	en_US
dc.format	Electronic	en_US
dc.language	eng	en_US
dc.publisher	BioMed Central	en_US
dc.relation.ispartof	Retrovirology	en_US
dc.relation.isbasedon	10.1186/1742-4690-10-159	en_US
dc.rights	info:eu-repo/semantics/openAccess
dc.subject.classification	Virology	en_US
dc.subject.mesh	T-Lymphocytes	en_US
dc.subject.mesh	Cell Line	en_US
dc.subject.mesh	Humans	en_US
dc.subject.mesh	Human T-lymphotropic virus 1	en_US
dc.subject.mesh	CCAAT-Enhancer-Binding Protein-alpha	en_US
dc.subject.mesh	Viral Proteins	en_US
dc.subject.mesh	DNA	en_US
dc.subject.mesh	Cell Proliferation	en_US
dc.subject.mesh	Protein Binding	en_US
dc.subject.mesh	Adult	en_US
dc.subject.mesh	Aged	en_US
dc.subject.mesh	Middle Aged	en_US
dc.subject.mesh	Female	en_US
dc.subject.mesh	Male	en_US
dc.subject.mesh	Basic-Leucine Zipper Transcription Factors	en_US
dc.subject.mesh	Host-Pathogen Interactions	en_US
dc.subject.mesh	Retroviridae Proteins	en_US
dc.title	HTLV-1 bZIP factor supports proliferation of adult T cell leukemia cells through suppression of C/EBPα signaling.	en_US
dc.type	Journal Article
utslib.citation.volume	10	en_US
utslib.for	1103 Clinical Sciences	en_US
pubs.embargo.period	Not known	en_US
utslib.copyright.status	open_access	*
pubs.declined	2017-09-18T15:57:30.598+1000
pubs.consider-herdc	false	en_US
pubs.publication-status	Published	en_US
pubs.volume	10	en_US

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.

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http://hdl.handle.net/10453/117262