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ATF3, an HTLV-1 bZip factor binding protein, promotes proliferation of adult T-cell leukemia cells
by
Matsuoka, Masao
, Hagiya, Keita
, Ohshima, Koichi
, Satou, Yorifumi
, Yasunaga, Jun-ichirou
in
Activating Transcription Factor 3 - genetics
/ Activating Transcription Factor 3 - metabolism
/ Antibodies
/ Basic-Leucine Zipper Transcription Factors - genetics
/ Basic-Leucine Zipper Transcription Factors - metabolism
/ Biomedical and Life Sciences
/ Biomedicine
/ Cancer
/ Cancer Research
/ Cell cycle
/ Cell Line
/ Cell Proliferation
/ Genes
/ Genetic aspects
/ Health aspects
/ HTLV-I (Virus)
/ Human T-lymphotropic virus 1 - genetics
/ Human T-lymphotropic virus 1 - metabolism
/ Human T-lymphotropic virus 1 - physiology
/ Humans
/ Immunoprecipitation
/ Infectious Diseases
/ Leukemia-Lymphoma, Adult T-Cell - pathology
/ Leukemia-Lymphoma, Adult T-Cell - virology
/ Physiological aspects
/ Protein Structure
/ Proteins
/ T-Lymphocytes
/ Transcription factors
/ Two-Hybrid System Techniques
/ Up-Regulation
/ Vaccine
/ Viral Proteins - genetics
/ Viral Proteins - metabolism
/ Virology
2011
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ATF3, an HTLV-1 bZip factor binding protein, promotes proliferation of adult T-cell leukemia cells
by
Matsuoka, Masao
, Hagiya, Keita
, Ohshima, Koichi
, Satou, Yorifumi
, Yasunaga, Jun-ichirou
in
Activating Transcription Factor 3 - genetics
/ Activating Transcription Factor 3 - metabolism
/ Antibodies
/ Basic-Leucine Zipper Transcription Factors - genetics
/ Basic-Leucine Zipper Transcription Factors - metabolism
/ Biomedical and Life Sciences
/ Biomedicine
/ Cancer
/ Cancer Research
/ Cell cycle
/ Cell Line
/ Cell Proliferation
/ Genes
/ Genetic aspects
/ Health aspects
/ HTLV-I (Virus)
/ Human T-lymphotropic virus 1 - genetics
/ Human T-lymphotropic virus 1 - metabolism
/ Human T-lymphotropic virus 1 - physiology
/ Humans
/ Immunoprecipitation
/ Infectious Diseases
/ Leukemia-Lymphoma, Adult T-Cell - pathology
/ Leukemia-Lymphoma, Adult T-Cell - virology
/ Physiological aspects
/ Protein Structure
/ Proteins
/ T-Lymphocytes
/ Transcription factors
/ Two-Hybrid System Techniques
/ Up-Regulation
/ Vaccine
/ Viral Proteins - genetics
/ Viral Proteins - metabolism
/ Virology
2011
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ATF3, an HTLV-1 bZip factor binding protein, promotes proliferation of adult T-cell leukemia cells
by
Matsuoka, Masao
, Hagiya, Keita
, Ohshima, Koichi
, Satou, Yorifumi
, Yasunaga, Jun-ichirou
in
Activating Transcription Factor 3 - genetics
/ Activating Transcription Factor 3 - metabolism
/ Antibodies
/ Basic-Leucine Zipper Transcription Factors - genetics
/ Basic-Leucine Zipper Transcription Factors - metabolism
/ Biomedical and Life Sciences
/ Biomedicine
/ Cancer
/ Cancer Research
/ Cell cycle
/ Cell Line
/ Cell Proliferation
/ Genes
/ Genetic aspects
/ Health aspects
/ HTLV-I (Virus)
/ Human T-lymphotropic virus 1 - genetics
/ Human T-lymphotropic virus 1 - metabolism
/ Human T-lymphotropic virus 1 - physiology
/ Humans
/ Immunoprecipitation
/ Infectious Diseases
/ Leukemia-Lymphoma, Adult T-Cell - pathology
/ Leukemia-Lymphoma, Adult T-Cell - virology
/ Physiological aspects
/ Protein Structure
/ Proteins
/ T-Lymphocytes
/ Transcription factors
/ Two-Hybrid System Techniques
/ Up-Regulation
/ Vaccine
/ Viral Proteins - genetics
/ Viral Proteins - metabolism
/ Virology
2011
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ATF3, an HTLV-1 bZip factor binding protein, promotes proliferation of adult T-cell leukemia cells
Journal Article
ATF3, an HTLV-1 bZip factor binding protein, promotes proliferation of adult T-cell leukemia cells
2011
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Overview
Background
Adult T-cell leukemia (ATL) is an aggressive malignancy of CD4
+
T-cells caused by human T-cell leukemia virus type 1 (HTLV-1). The
HTLV-1 bZIP factor
(
HBZ
) gene, which is encoded by the minus strand of the viral genome, is expressed as an antisense transcript in all ATL cases. By using yeast two-hybrid screening, we identified activating transcription factor 3 (ATF3) as an HBZ-interacting protein. ATF3 has been reported to be expressed in ATL cells, but its biological significance is not known.
Results
Immunoprecipitation analysis confirmed that ATF3 interacts with HBZ. Expression of ATF3 was upregulated in ATL cell lines and fresh ATL cases. Reporter assay revealed that ATF3 could interfere with the HTLV-1 Tax's transactivation of the 5' proviral long terminal repeat (LTR), doing so by affecting the ATF/CRE site, as well as HBZ. Suppressing ATF3 expression inhibited proliferation and strongly reduced the viability of ATL cells. As mechanisms of growth-promoting activity of ATF3, comparative expression profiling of ATF3 knockdown cells identified candidate genes that are critical for the cell cycle and cell death, including cell division cycle 2 (CDC2) and cyclin E2. ATF3 also enhanced p53 transcriptional activity, but this activity was suppressed by HBZ.
Conclusions
Thus, ATF3 expression has positive and negative effects on the proliferation and survival of ATL cells. HBZ impedes its negative effects, leaving ATF3 to promote proliferation of ATL cells via mechanisms including upregulation of CDC2 and cyclin E2. Both HBZ and ATF3 suppress Tax expression, which enables infected cells to escape the host immune system.
Publisher
BioMed Central,BioMed Central Ltd,Springer Nature B.V,BMC
Subject
Activating Transcription Factor 3 - genetics
/ Activating Transcription Factor 3 - metabolism
/ Basic-Leucine Zipper Transcription Factors - genetics
/ Basic-Leucine Zipper Transcription Factors - metabolism
/ Biomedical and Life Sciences
/ Cancer
/ Genes
/ Human T-lymphotropic virus 1 - genetics
/ Human T-lymphotropic virus 1 - metabolism
/ Human T-lymphotropic virus 1 - physiology
/ Humans
/ Leukemia-Lymphoma, Adult T-Cell - pathology
/ Leukemia-Lymphoma, Adult T-Cell - virology
/ Proteins
/ Two-Hybrid System Techniques
/ Vaccine
/ Virology
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