Control of cAMP-regulated enhancers by the viral transactivator Tax through CREB and the co-activator CBP

Kwok, Roland P.S.; Laurance, Megan E.; Lundblad, James R.; Goldman, Phyllis S.; Shih, Hsiu‐Ming; Connor, Laurie; Marriott, Susan J.; Goodman, Richard H.

doi:10.1038/380642a0

Cited by 341 publications

(389 citation statements)

References 22 publications

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“…Given that binding to the co-activators is critical for Tax1 and Tax2-mediated transactivation (Kwok et al, 1996;Harrod et al, 1998;Kashanchi et al, 1998;Meertens et al, 2004b), we also undertook a series of experiments aiming at determining whether Tax3 could bind the CBP and p300 coactivators. Using the GFP, GFP-Tax1, GFP-Tax2 and GFP-Tax3 S proteins Characterization of the HTLV/STLV-3 Tax protein SA Chevalier et al expressed from 293T-transfected cells, we performed a series of co-immunoprecipitations as previously described (Meertens et al, 2004b).…”

Section: Resultsmentioning

confidence: 99%

The tax protein from the primate T-cell lymphotropic virus type 3 is expressed in vivo and is functionally related to HTLV-1 Tax rather than HTLV-2 Tax

et al. 2006

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Human T-cell leukemia virus and simian T-cell leukemia virus (STLV) form the primate T-cell lymphotropic viruses group. Human T-cell leukemia virus type 1 and type 2 (HTLV-1 and HTLV-2) encode the Tax viral transactivator (Tax1 and Tax2, respectively). Tax1 possesses an oncogenic potential and is responsible for cell transformation both in vivo and in vitro. We and others have recently discovered the existence of human Tcell lymphotropic virus type 3. However, there is currently no evidence for the presence of a Tax protein in HTLV-3-infected individuals. We show that the serum of an HTLV-3 asymptomatic carrier and the sera of two STLV-3-infected monkeys contain specific anti-Tax3 antibodies. We also show that tax3 mRNA is present in the PBMCs obtained from an STLV-3-infected monkey, demonstrating that Tax3 is expressed in vivo. We further demonstrate that Tax3 intracellular localization is very similar to that of Tax1 and that Tax3 binds to both CBP and p300 coactivators. Using purified Tax3, we show that the protein increases transcription from a 4TxRE G-free cassette plasmid in an in vitro transcription assay. In all cell types tested, including transiently transfected lymphocytes, Tax3 activates its own promoter STLV-3 long terminal repeat (LTR), which contains only two Tax Responsive Elements (TREs), and activates also HTLV-1 and HTLV-2 LTRs. In addition, Tax3 also activates the NF-jB pathway. We also show that Tax3 possesses a PDZ-binding sequence at its C-terminal end. Our results demonstrate that Tax3 is a transactivator, and that its properties are more similar to that of Tax1, rather than of Tax2. This suggests the possible occurrence of lymphoproliferative disorders among HTLV-3-infected populations.

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Section: Resultsmentioning

confidence: 99%

The tax protein from the primate T-cell lymphotropic virus type 3 is expressed in vivo and is functionally related to HTLV-1 Tax rather than HTLV-2 Tax

et al. 2006

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“…Previous studies have shown that c-Myb and Tax proteins interact with the same region of CBP in a signal-independent manner, amino acid residues 461 ± 661 and 451 ± 682, respectively (Dai et al, 1996;Oelgeschlager et al, 1996;Kwok et al, 1996). Because c-Myb can transactivate its own promoter in Jurkat T-cells (Figure 1c), we tested whether competition between c-Myb and Tax for the recruitment of CBP or p300 could explain Tax-mediated repression of the c-Myb promoter.…”

Section: Repression Of the C-myb Promoter By The Tax Protein Through mentioning

confidence: 97%

HTLV-I Tax transrepresses the human c-Myb promoter independently of its interaction with CBP or p300

et al. 2000

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“…Since Tax is reported to bind to CBP/p300 (Bex et al, 1998;Kwok et al, 1996), we examined the possibility that Tax binding to CBP/p300 a ects its function in these two systems.…”

Section: Inhibition Of Cbp/p300-directed Transcription By Taxmentioning

confidence: 99%

“…Furthermore, Tax interacts with a transcriptional coactivator, CBP, which binds to the phosphorylated form of CREB (Chrivia et al, 1993). Through these binding capacities, Tax functions as a linker between CREB and CBP in a phosphorylation-independent manner on the viral enhancer, the 21-bp element (Giebler et al, 1997;Harrod et al, 1998;Kwok et al, 1996;Lenzmeier et al, 1998).…”

Section: Introductionmentioning

confidence: 99%

Tax protein of HTLV-1 inhibits CBP/p300-mediated transcription by interfering with recruitment of CBP/p300 onto DNA element of E-box or p53 binding site

1999

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Tax protein of human T-cell leukemia virus type 1 (HTLV-1) is a potent transcriptional regulator which can activate or repress speci®c cellular genes and has been proposed to contribute to leukemogenic processes in adult T-cell leukemia. The molecular mechanism of Taxmediated trans-activation has been well investigated. However, trans-repression by Tax remains to be studied in detail, although it is known to require a speci®c DNA element such as E-box or p53 binding site. Examining possible mechanisms of trans-repression, we found that co-expression of E47 and p300 activated E-box dependent transcription and this activation was e ciently repressed by Tax. In this system, Tax bound to p300 and decreased the level of p300 complexed on the E-box element. Similarly, Tax inhibited transcription directed by p53 and CBP, reducing the level of CBP on the p53 binding site. These results indicate that Tax interferes with recruitment of CBP/p300 into protein complexes on E-box and p53 binding site through its binding to CBP/ p300. In contrast to these ®ndings, we observed that Tax increased the level of CBP on the viral 21-bp enhancer which is trans-activated by Tax. From these observations, we propose a universal mechanism for Taxmediated trans-repression and trans-activation of transcription in which Tax binds to CBP/p300 and determines the accessibility of CBP/p300 to protein complexes on speci®c DNA element.

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Control of cAMP-regulated enhancers by the viral transactivator Tax through CREB and the co-activator CBP

Cited by 341 publications

References 22 publications

The tax protein from the primate T-cell lymphotropic virus type 3 is expressed in vivo and is functionally related to HTLV-1 Tax rather than HTLV-2 Tax

The tax protein from the primate T-cell lymphotropic virus type 3 is expressed in vivo and is functionally related to HTLV-1 Tax rather than HTLV-2 Tax

HTLV-I Tax transrepresses the human c-Myb promoter independently of its interaction with CBP or p300

Tax protein of HTLV-1 inhibits CBP/p300-mediated transcription by interfering with recruitment of CBP/p300 onto DNA element of E-box or p53 binding site

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