p300 and p300/cAMP-responsive Element-binding Protein Associated Factor Interact with Human T-cell Lymphotropic Virus Type-1 Tax in a Multi-histone Acetyltransferase/Activator-Enhancer Complex

Harrod, Robert; Kuo, Yu‐Liang; Tang, Yong; Yao, Yao; Vassilev, Alex; Nakatani, Yoshihiro; Giam, Chou-Zen

doi:10.1074/jbc.275.16.11852

Cited by 105 publications

(121 citation statements)

References 65 publications

(85 reference statements)

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“…Our studies demonstrate that CBP and p300, but not PCAF, enhance Tax-2-directed LTR transactivation. The fact that PCAF, p300, and CBP all are essential for optimal transactivation by Tax-1 (23)(24)(25) substantiates the existence of important differences between HTLV-2 Tax-2 and HTLV-1 Tax-1. The different requirement for PCAF between the two viral transactivators also implies that Tax-1, but not Tax-2, might influence nuclear PCAF-containing complexes, potentially contributing to the pleiotropic deregulated expression of cellular genes during leukemogenesis.…”

Section: Discussionmentioning

confidence: 98%

“…This interaction stabilizes the complex and facilitates the recruitment of general transcription factors and coactivators, such as the histone acetyltransferases (HATs), CBP, p300, and p300͞CBP-associated factor (PCAF), resulting in the enhancement of transcription (21)(22)(23)(24)(25)(26). Tax-1 also deregulates the expression of a variety of cellular genes and signaling pathways involved in cell cycle progression, cell growth, DNA repair, and apoptosis.…”

mentioning

confidence: 99%

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Inhibition of human T cell leukemia virus type 2 replication by the suppressive action of class II transactivator and nuclear factor Y

Tosi

Pilotti

Mortara

et al. 2006

Proc. Natl. Acad. Sci. U.S.A.

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The master regulator of MHC-II gene transcription, class II transactivator (CIITA), acts as a potent inhibitor of human T cell leukemia virus type 2 (HTLV-2) replication by blocking the activity of the viral Tax-2 transactivator. Here, we show that this inhibitory effect takes place at the nuclear level and maps to the N-terminal 1-321 region of CIITA, where we identified a minimal domain, from positions 64 -144, that is strictly required to suppress Tax-2 function. Furthermore, we show that Tax-2 specifically cooperates with cAMP response element binding protein-binding protein (CBP) and p300, but not with p300͞CBP-associated factor, to enhance transcription from the viral promoter. This finding represents a unique difference with respect to Tax-1, which uses all three coactivators to transactivate the human T cell leukemia virus type 1 LTR. Direct sequestering of CBP or p300 is not the primary mechanism by which CIITA causes suppression of Tax-2. Interestingly, we found that the transcription factor nuclear factor Y, which interacts with CIITA to increase transcription of MHC-II genes, exerts a negative regulatory action on the Tax-2-mediated HTLV-2 LTR transactivation. Thus, CIITA may inhibit Tax-2 function, at least in part, through nuclear factor Y. These findings demonstrate the dual defensive role of CIITA against pathogens: it increases the antigen-presenting function for viral determinants and suppresses HTLV-2 replication in infected cells. Tax-2 MHC class II ͉ viral replication ͉

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Section: Discussionmentioning

confidence: 98%

mentioning

confidence: 99%

Inhibition of human T cell leukemia virus type 2 replication by the suppressive action of class II transactivator and nuclear factor Y

Tosi

Pilotti

Mortara

et al. 2006

Proc. Natl. Acad. Sci. U.S.A.

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“…Tax does not directly bind DNA, but associates through its N-terminus with the CREB protein (Baranger et al, 1995;Adya and Giam, 1995), which docks at the LTR's cyclic-AMP responsive (CRE)-motifs. Tax also recruits transcriptional coactivators, CBP and p300 (Giebler et al, 1997;Bex et al, 1998;Harrod et al, 2000), and in a lessdefined manner, P/CAF (Okada and Jeang, 2002). The C-terminal activation domain of Tax (Semmes and Jeang, 1995) is thought to directly contact the TATAbox-bound TBP protein (Caron et al, 1993) thereby promoting transcriptional initiation and RNA polymerase elongation (Ching et al, 2004).…”

Section: Structure-function Features Of Tax For Transcriptional Activmentioning

confidence: 99%

Molecular mechanisms of cellular transformation by HTLV-1 Tax

2005

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“…Recent data have also indicated that the PI3K-Akt pathway in the interaction with CREB/ATF-1 (1, 8,152,199,204,205), CBP/p300 (12,58,59,99,106), and the Tax-responsive 21-bp repeat element, and activates the NF-!B pathway (26,44,82,178,187,194). In addition to its transactivation functions, Tax also impacts on many aspects of the cell cycle (90,96,108,111,112,118,145).…”

Section: Nf-!b Activation By Tax Is Not Sufficient For the Transformamentioning

confidence: 99%

“…The HTLV-1 viral transactivator/onco-protein Tax is thought to play an important role in T-cell malignancy and HAM/TSP. Tax transactivates the HTLV-1 LTR promoter through its interaction with CREB/ATF-1 (1, 8,152,199,204,205), CBP/p300 (12,58,59,99,106), and the Tax-responsive 21-bp repeat element, and activates the NF-!B pathway (26,82,178,187,192,194) through the interaction with PP2A/IKK" (44). In addition to its transactivation functions, Tax also impacts on many aspects of the cell cycle: activating G 1 /S transition (90,118,145), inactivating p53 functions (158), inducing p21 CIP1/WAF1 mRNA transcription (2,24,33,89), and inhibiting apoptosis and DNA repair (87,104).…”

Section: Introductionmentioning

confidence: 99%

HTLV-1 Tax Effects on Cellular Mitotic Regulation

Merling¹

2007

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The human T-cell leukemia virus 1 (HTLV-1) encodes the tax gene (transactivator encoded by the pX region) which is a potent activator of viral transcription and Nuclear , this cyclin-dependent kinase inhibitor may also play a role in tax-IRS.As part of the research presented in this dissertation, a collection of HTLV-1 tax point mutants were isolated that permit normal growth of S. cerevisiae. Similar to wild-type tax, many mutants (C23W, A108T, L159F, and L235F) transactivated both the HTLV long terminal repeat (LTR) and the NF-!B reporters. The V19M mutant preferentially activated NF-!B, but was attenuated in LTR activation. None of the mutants significantly elevated the levels of p21 CIP1/WAF1 and p27 KIP1 , indicating that dramatic Tax-induced surges in p21and p27 KIP1 occurs by mechanisms distinct from NF-!B and LTR activation. Importantly, the ability of these mutants to activate APC was attenuated or abrogated. These data show that Tax-induced rapid senescence is causally associated with APC activation and suggest iv that the mitotic abnormalities that are associated with premature APC activation might play an important role in cell transformation by Tax.In a parallel study, we demonstrate that Tax interacts with both centrosomal Nek2-associated protein 1 (C-Nap1), a large coiled-coil protein that maintains centrosome cohesion, and protein phosphatase 1 (PP1) and that these interactions localize to the centrosome. Furthermore, in cells expressing tax, C-Nap1 phosphorylation is greatly diminished. C-Nap1 phosphorylation status plays an important role in centrosome cycle progression; PP1-mediated dephosphorylation of C-Nap1 maintains centriolar cohesion during interphase, and never in mitosis A (NIMA)-related kinase 2 (Nek2A)-mediated phosphorylation of C-Nap1 during G2/M triggers C-Nap1 dissociation from duplicated centrosomes permitting normal centrosome disjunction. Our data suggest that Tax, through recruitment of PP1 to C-Nap1, may permit prolonged C-Nap1 dephosphorylation thereby disrupting normal centrosome disjunction leading to observed Tax-induced centrosome abnormalities and distinct microtubule organizing center (MTOC) loss.Our studies have revealed two distinct pathways through which Tax could contribute to oncogenesis. First, our Tax mutants that retained LTR and NF-!B activation properties but were impaired in APC activation were also defective in the ability to transform Rat1 fibroblasts. Therefore, premature APC activation by Tax appears to correlate with the ability of Tax to induce cellular transformation. Second, our demonstration of Tax-mediated alterations in C-Nap1 phosphorylation cycle offers an explanation for the centrosome abnormalities and mitotic apparatus defects observed in response to Tax expression.Chromosomal abnormalities resulting from such mitotic apparatus defects may be expected to contribute to the oncogenic potential of Tax.v

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p300 and p300/cAMP-responsive Element-binding Protein Associated Factor Interact with Human T-cell Lymphotropic Virus Type-1 Tax in a Multi-histone Acetyltransferase/Activator-Enhancer Complex

Cited by 105 publications

References 65 publications

Inhibition of human T cell leukemia virus type 2 replication by the suppressive action of class II transactivator and nuclear factor Y

Inhibition of human T cell leukemia virus type 2 replication by the suppressive action of class II transactivator and nuclear factor Y

Molecular mechanisms of cellular transformation by HTLV-1 Tax

HTLV-1 Tax Effects on Cellular Mitotic Regulation

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