Document Detail

Complex cell cycle abnormalities caused by human T-lymphotropic virus type 1 Tax.
MedLine Citation:
PMID:  21209109     Owner:  NLM     Status:  MEDLINE    
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.
Liangpeng Yang; Naoe Kotomura; Yik-Khuan Ho; Huijun Zhi; Sandra Bixler; Michael J Schell; Chou-Zen Giam
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2011-01-05
Journal Detail:
Title:  Journal of virology     Volume:  85     ISSN:  1098-5514     ISO Abbreviation:  J. Virol.     Publication Date:  2011 Mar 
Date Detail:
Created Date:  2011-02-18     Completed Date:  2011-04-11     Revised Date:  2013-07-03    
Medline Journal Info:
Nlm Unique ID:  0113724     Medline TA:  J Virol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  3001-9     Citation Subset:  IM    
Department of Microbiology and Immunology, Uniformed Services University of the Health Sciences, 4301 Jones Bridge Rd., Bethesda, MD 20814, USA.
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MeSH Terms
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*
Microscopy, Video
Grant Support
Reg. No./Substance:
0/Gene Products, tax; 0/enhanced green fluorescent protein; 0/tax protein, Human T-lymphotrophic virus 1; 147336-22-9/Green Fluorescent Proteins

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