Human T-Cell Leukemia Virus Type I Tax Transactivates the Promoter of Human Prointerleukin-1β Gene Through Association With Two Transcription Factors, Nuclear Factor–Interleukin-6 and Spi-1

Tsukada, Junichi; Misago, M; Serino, Yoko; Ogawa, Ryo; Murakami, S; Nakanishi, Masatsugu; Tonai, Shinichi; Kominato, Yoshihiko; Morimoto, Isao; Auron, Philip E.; Eto, Sumiya

doi:10.1182/blood.v90.8.3142

Cited by 35 publications

(18 citation statements)

References 60 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…We have also studied the role of the PU.1/Spi-B site in the regulation of BLV-directed gene expression in presence of Tax BLV . Indeed, a direct interaction between PU.1 and the viral transactivator Tax HTLV has been previously reported in the context of the IL1B promoter (Tsukada et al, 1997). However, our data showed that mutation of the BLV PU.1/Spi-B binding site did not affect the transactivation by Tax BLV .…”

Section: Discussioncontrasting

confidence: 54%

Identification and characterization of a PU.1/Spi-B binding site in the bovine leukemia virus long terminal repeat

et al. 2003

View full text Add to dashboard Cite

Bovine leukemia virus (BLV) is a B-lymphotropic oncogenic retrovirus whose transcriptional promoter is located in the viral 5' long terminal repeat (LTR). To date, no B-lymphocyte-specific cis-regulatory element has been identified in this region. Since ETS proteins are known to regulate transcription of numerous retroviruses, we searched for the presence in the BLV promoter region of binding sites for PU.1/Spi-1, a B-cell- and macrophage-specific ETS family member. In this report, nucleotide sequence analysis of the viral LTR identified a PUbox located at -95/-84 bp. We demonstrated by gel shift and supershift assays that PU.1 and the related Ets transcription factor Spi-B interacted specifically with this PUbox. A 2-bp mutation (GGAA-->CCAA) within this motif abrogated PU.1/Spi-B binding. This mutation caused a marked decrease in LTR-driven basal gene expression in transient transfection assays of B-lymphoid cell lines, but did not impair the responsiveness of the BLV promoter to the virus-encoded transactivator Tax(BLV). Moreover, ectopically expressed PU.1 and Spi-B proteins transactivated the BLV promoter in a PUbox-dependent manner. Taken together, our results provide the first demonstration of regulation of the BLV promoter by two B-cell-specific Ets transcription factors, PU.1 and Spi-B. The PU.1/Spi-B binding site identified here could play an important role in BLV replication and B-lymphoid tropism.

show abstract

Section: Discussioncontrasting

confidence: 54%

Identification and characterization of a PU.1/Spi-B binding site in the bovine leukemia virus long terminal repeat

et al. 2003

View full text Add to dashboard Cite

show abstract

“…In addition, NF‐IL6 is heterodimerized with members of the C/EBP family and the AP‐1 family through their bZIP regions and is also associated with several transcription factors outside the bZIP family members such as NF‐κB (Stein et al . 1993), Tax (Tsukada et al . 1997), PU.1 (Yang et al .…”

Section: Discussionmentioning

confidence: 99%

Intracellular galectin‐9 activates inflammatory cytokines in monocytes

et al. 2009

Self Cite

View full text Add to dashboard Cite

Whether galectin-9 plays a role in inflammatory responses remains elusive. The present study was designed to determine the role of intracellular galectin-9 in activation of inflammatory cytokine genes in human monocytes. Galectin-9 expression vector pBKCMV3-G9 was transiently cotransfected into THP-1 monocytic cells along with luciferase reporters carrying gene promoters of IL-1α (IL1A), IL-1β (IL1B) and IFNγ. Transient transfection studies showed that galectin-9 over-expression activated all three gene promoters, suggesting that intracellular galectin-9 induces inflammatory cytokine genes in monocytes. Galectin-9 over-expression also activated NF-IL6 (C/EBP β) and AP-1, but not NF-κB. In contrast, extracellular galectin-9 is not involved in regulation of inflammatory cytokines. Immunoprecipitation/Western blotting, using anti-galectin-9 Ab and anti-NF-IL6 Ab, showed physical association of intracellular galectin-9 with NF-IL6. RT-PCR confirmed that galectin-9 over-expression increased IL-1α and IL-1β mRNA levels in THP-1 cells. The interaction of galectin-9 with NF-IL6 was enhanced following LPS treatment in THP-1 cells. Intracellular galectin-9 synergized with LPS to activate NF-IL6. Nuclear translocation of galectin-9 was also observed in THP-1 cells treated with LPS. Our results indicate that galectin-9 is a LPSresponsive factor, and further demonstrate that intracellular galectin-9 transactivates inflammatory cytokine genes in monocytes through direct physical interaction with NF-IL6.

show abstract

“…Thus, the recruiting of Tax directly to unphosphorylated CREB-2 bound to cellular promoters could allow a stimulation of cellular transcription independently of cellular activation. Moreover, CREB-2 is known to heterodimerize with many bZIP transcription factors, such as ATF-1, ATF-2, ATF-3, C/EBP␣, -␤, -␦, -ε, -␥, and -, c-Fos, c-Jun, JunB, JunD, Fra-1, and GPE1-BP (14,18,31,42,59,79,80), and several of these factors have been described to be involved in transactivation of cellular gene transcription in cooperation with Tax (17,19,20,51,78,83). It is tempting to speculate that CREB-2 could stimulate Tax-mediated transcription of the viral and cellular genes in association with these different factors.…”

Section: Discussionmentioning

confidence: 99%

Molecular Interactions Involved in the Transactivation of the Human T-Cell Leukemia Virus Type 1 Promoter Mediated by Tax and CREB-2 (ATF-4)

Gachon¹,

Thebault

Péleraux

et al. 2000

Mol. Cell. Biol.

View full text Add to dashboard Cite

The human T-cell leukemia virus type 1 (HTLV-1) Tax protein activates viral transcription through three 21-bp repeats located in the U3 region of the HTLV-1 long terminal repeat and called Tax-responsive elements (TxREs). Each TxRE contains nucleotide sequences corresponding to imperfect cyclic AMP response elements (CRE). In this study, we demonstrate that the bZIP transcriptional factor CREB-2 is able to bind in vitro to the TxREs and that CREB-2 binding to each of the 21-bp motifs is enhanced by Tax. We also demonstrate that Tax can weakly interact with CREB-2 bound to a cellular palindromic CRE motif such as that found in the somatostatin promoter. Mutagenesis of Tax and CREB-2 demonstrates that both N-and C-terminal domains of Tax and the C-terminal region of CREB-2 are required for direct interaction between the two proteins. In addition, the Tax mutant M47, defective for HTLV-1 activation, is unable to form in vitro a ternary complex with CREB-2 and TxRE. In agreement with recent results suggesting that Tax can recruit the coactivator CREB-binding protein (CBP) on the HTLV-1 promoter, we provide evidence that Tax, CREB-2, and CBP are capable of cooperating to stimulate viral transcription. Taken together, our data highlight the major role played by CREB-2 in Tax-mediated transactivation.

show abstract

Human T-Cell Leukemia Virus Type I Tax Transactivates the Promoter of Human Prointerleukin-1β Gene Through Association With Two Transcription Factors, Nuclear Factor–Interleukin-6 and Spi-1

Cited by 35 publications

References 60 publications

Identification and characterization of a PU.1/Spi-B binding site in the bovine leukemia virus long terminal repeat

Identification and characterization of a PU.1/Spi-B binding site in the bovine leukemia virus long terminal repeat

Intracellular galectin‐9 activates inflammatory cytokines in monocytes

Molecular Interactions Involved in the Transactivation of the Human T-Cell Leukemia Virus Type 1 Promoter Mediated by Tax and CREB-2 (ATF-4)

Contact Info

Product

Resources

About