| Complex cell cycle abnormalities caused by human T-lymphotropic virus type 1 Tax. | |
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MedLine Citation:
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PMID: 21209109 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Human T-lymphotropic virus type 1 (HTLV-1) is the causative agent of adult T-cell leukemia/lymphoma (ATL), a malignancy of CD4(+) T cells whose etiology is thought to be associated with the viral trans-activator Tax. We have shown recently that Tax can drastically upregulate the expression of p27(Kip1) and p21(CIP1/WAF1) through protein stabilization and mRNA trans-activation and stabilization, respectively. The Tax-induced surge in p21(CIP1/WAF1) and p27(Kip1) begins in S phase and results in cellular senescence. Importantly, HeLa and SupT1 T cells infected by HTLV-1 also arrest in senescence, thus challenging the notion that HTLV-1 infection causes cell proliferation. Here we use time-lapse microscopy to investigate the effect of Tax on cell cycle progression in two reporter cell lines, HeLa/18x21-EGFP and HeLa-FUCCI, that express enhanced green fluorescent protein (EGFP) under the control of 18 copies of the Tax-responsive 21-bp repeat element and fluorescent ubiquitin cell cycle indicators, respectively. Tax-expressing HeLa cells exhibit elongated or stalled cell cycle phases. Many of them bypass mitosis and become single senescent cells as evidenced by the expression of senescence-associated β-galactosidase. Such cells have twice the normal equivalent of cellular contents and hence are enlarged, with exaggerated nuclei. Interestingly, nocodazole treatment revealed a small variant population of HeLa/18x21-EGFP cells that could progress into mitosis normally with high levels of Tax expression, suggesting that genetic or epigenetic changes that prevent Tax-induced senescence can occur spontaneously at a detectable frequency. |
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Authors:
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Liangpeng Yang; Naoe Kotomura; Yik-Khuan Ho; Huijun Zhi; Sandra Bixler; Michael J Schell; Chou-Zen Giam |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural Date: 2011-01-05 |
Journal Detail:
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Title: Journal of virology Volume: 85 ISSN: 1098-5514 ISO Abbreviation: J. Virol. Publication Date: 2011 Mar |
Date Detail:
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Created Date: 2011-02-18 Completed Date: 2011-04-11 Revised Date: 2011-09-13 |
Medline Journal Info:
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Nlm Unique ID: 0113724 Medline TA: J Virol Country: United States |
Other Details:
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Languages: eng Pagination: 3001-9 Citation Subset: IM |
Affiliation:
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Department of Microbiology and Immunology, Uniformed Services University of the Health Sciences, 4301 Jones Bridge Rd., Bethesda, MD 20814, USA. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Artificial Gene Fusion Cell Cycle / physiology* Gene Products, tax / metabolism* Genes, Reporter Green Fluorescent Proteins / genetics, metabolism Hela Cells Human T-lymphotropic virus 1 / pathogenicity* Humans Microscopy, Video |
| Grant Support | |
ID/Acronym/Agency:
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1S10RR019083/RR/NCRR NIH HHS; R01CA115884/CA/NCI NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Gene Products, tax; 0/enhanced green fluorescent protein; 0/tax protein, Human T-lymphotrophic virus 1; 147336-22-9/Green Fluorescent Proteins |
| Comments/Corrections | |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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