Characterization of peripheral blood T-lymphocytes transduced with HTLV-I Tax mutants with different trans-activating phenotypes

Akagi, Tsuyoshi; Ono, Hiroaki; Nyunoya, Hiroshi; Shimotohno, Kunitada

doi:10.1038/sj.onc.1201045

Cited by 101 publications

(117 citation statements)

References 24 publications

Supporting

Mentioning

114

Contrasting

Order By: Relevance

“…We, as well as others, have previously shown that p21 Waf1 expression is increased in HTLV-Iinfected T-cells and that Tax can induce its expression in a p53-independent manner (Akagi et al, 1996;Cereseto et al, 1996). Increasing amounts of p21 Waf1 correlated with constitutive activation of the cyclin E complex, suggesting that, at a particular stoichiometry, p21 Waf1 may lower the activation threshold of the cyclin E-CDK2 complex (La Baer et al, 1997;Macleod et al, 1995;Zhang et al, 1994).…”

Section: Discussionmentioning

confidence: 54%

See 1 more Smart Citation

Limiting amounts of p27Kip1 correlates with constitutive activation of cyclin E-CDK2 complex in HTLV-I-transformed T-cells

et al. 1999

View full text Add to dashboard Cite

Section: Discussionmentioning

confidence: 54%

“…In contrast, p21 Waf1 was consistently found highly expressed in HTLV-I-infected T-cells regardless of their requirement for IL-2 and presumably the viral transactivator Tax contributes to maintain high level of p21 mRNA (Akagi et al, 1996;Cereseto et al, 1996).…”

Section: P27 Kip1 Expression In Htlv-i-infected T-cell Linesmentioning

confidence: 87%

Limiting amounts of p27Kip1 correlates with constitutive activation of cyclin E-CDK2 complex in HTLV-I-transformed T-cells

et al. 1999

View full text Add to dashboard Cite

“…In addition to upregulating cyclin synthesis, Tax directly binds to cyclin D3, cyclin D2, and Cdk4 and stabilizes cyclin D/Cdk4 complexes (Haller et al, 2002). There have also been reports that Tax expression activates transcription of cdk2 and cdk4 , and represses transcription of CDKIs p18 INK4c and p19 INK4d (Akagi et al, 1996). Additionally, Tax can directly bind the CDKI p16 INK4a , thereby preventing it from binding to Cdk4 and Cdk6 (Low et al, 1997).…”

Section: G 1 Phase and The G 1 /S Transitionmentioning

confidence: 99%

Impact of HTLV-I Tax on cell cycle progression and the cellular DNA damage repair response

2005

View full text Add to dashboard Cite

“…HTLV exerts its transforming capacity mainly through the viral oncoprotein Tax. This protein capably immortalizes human T cells (Akagi et al, 1997;Schmitt et al, 1998) and is leukaemogenic in transgenic mice (Grossman et al, 1995;Hasegawa et al, 2006). Proliferation of infected cells is enhanced by Tax by stimulating the G 1 to S phase transition, which is mediated by directly binding and activating cyclin-dependent kinase Cdk4/6 holoenzymes (Fraedrich et al, 2005;Haller et al, 2002; Neuveut et al, 1998).…”

Section: Introductionmentioning

confidence: 99%

Stimulation of interleukin-13 expression by human T-cell leukemia virus type 1 oncoprotein Tax via a dually active promoter element responsive to NF-κB and NFAT

Silbermann

Schneider

Grassmann

2008

Journal of General Virology

View full text Add to dashboard Cite

The human T-cell leukemia virus type 1 (HTLV-1) Tax oncoprotein transforms human lymphocytes and is critical for the pathogenesis of HTLV-1-induced adult T-cell leukaemia. In HTLVtransformed cells, Tax upregulates interleukin (IL)-13, a cytokine with proliferative and antiapoptotic functions that is linked to leukaemogenesis. Tax-stimulated IL-13 is thought to result in autocrine stimulation of HTLV-infected cells and thus may be relevant to their growth. The causal transactivation of the IL-13 promoter by Tax is predominantly dependent on a nuclear factor of activated T cells (NFAT)-binding P element. Here, it was shown that the isolated IL-13 Taxresponsive element (IL13TaxRE) was sufficient to mediate IL-13 transactivation by Tax and NFAT1. However, cyclosporin A, a specific NFAT inhibitor, revealed that Tax transactivation of IL13TaxRE or wild-type IL-13 promoter was independent of NFAT and that NFAT did not contribute to IL-13 upregulation in HTLV-transformed cells. By contrast, Tax stimulation was repressible by an efficient nuclear factor (NF)-kB inhibitor (IkBaDN), indicating the requirement for NF-kB. The capacity of NF-kB to stimulate IL13TaxRE was demonstrated by a strong response to NF-kB in reporter assays and by direct binding of NF-kB to IL13TaxRE. Thus, IL13TaxRE in the IL-13 promoter represents a dually active promoter element responsive to NF-kB and NFAT. Together, these results indicate that Tax causes IL-13 upregulation in HTLV-1-infected cells via NF-kB. INTRODUCTIONHuman T-cell leukemia virus type 1 (HTLV-1), a deltaretrovirus, is the aetiological agent of a severe malignancy of CD4 + T cells, adult T-cell leukaemia (ATL), and of a neurodegenerative, inflammatory disease of the spinal cord, HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) (Gessain et al., 1985; Poiesz et al., 1980;Yoshida et al., 1984). After primary infection, HTLV establishes life-long persistence and replicates mainly as integrated provirus. Viral persistence is characterized by long-lasting HTLV-infected T-cell clones, even in non-leukaemic patients. The clonal amplification of infected T cells and the capacity of these cells to establish permanent growth in culture suggest a growth-stimulating viral function that actively supports the replication of infected cells.Besides structural proteins, the proviral HTLV-1 genome encodes the regulatory proteins Rex and Tax, which are essential for the virus life cycle. The accessory proteins p12, p13 and p30 are important for viral infectivity and replication but are dispensable for transformation. An HTLV-1-encoded minus-strand gene encoding the HBZ protein is probably relevant to the pathogenesis of ATL (Yasunaga & Matsuoka, 2007). HTLV exerts its transforming capacity mainly through the viral oncoprotein Tax. This protein capably immortalizes human T cells (Akagi et al., 1997;Schmitt et al., 1998) and is leukaemogenic in transgenic mice (Grossman et al., 1995;Hasegawa et al., 2006). Proliferation of infected cells is enhanced by Tax by stimulating the G 1 to...

show abstract

Characterization of peripheral blood T-lymphocytes transduced with HTLV-I Tax mutants with different trans-activating phenotypes

Cited by 101 publications

References 24 publications

Limiting amounts of p27Kip1 correlates with constitutive activation of cyclin E-CDK2 complex in HTLV-I-transformed T-cells

Limiting amounts of p27Kip1 correlates with constitutive activation of cyclin E-CDK2 complex in HTLV-I-transformed T-cells

Impact of HTLV-I Tax on cell cycle progression and the cellular DNA damage repair response

Stimulation of interleukin-13 expression by human T-cell leukemia virus type 1 oncoprotein Tax via a dually active promoter element responsive to NF-κB and NFAT

Contact Info

Product

Resources

About