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CNTN2 — NFKB1

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Mori et al., Blood 1999 (Leukemia-Lymphoma, Adult T-Cell) : The viral protein Tax induces the activation and nuclear translocalization of transcription factor NF-kappaB , which is proposed to play a crucial role in the transformation of T cells by HTLV-I
Jin et al., J Biol Chem 1999 : Mechanisms by which the human T-cell leukemia virus type I Tax oncoprotein activates NF-kappaB remain incompletely understood ... This direct interaction with IKK-gamma correlates with Tax induced IkappaB-alpha phosphorylation and NF-kappaB activation
Arima et al., Exp Hematol 1999 (Acute Disease...) : Tax induction of NF-kappaB is presumed to be involved in proliferation and activation of primary leukemia cells in vivo
Li et al., Gene Expr 1999 : Tax also induces a variety of cellular genes through activation of the transcription factor NF-kappaB
Sun et al., Oncogene 1999 : As reviewed here, Tax activates NF-kappaB primarily via a pathway leading to the chronic phosphorylation and degradation of IkappaBalpha, a cytoplasmic inhibitor of NF-kappaB
Pise-Masison et al., Mol Cell Biol 2000 : Analysis of Tax mutants demonstrated that Tax inactivation of p53 function correlates with the ability of Tax to induce NF-kappaB but not p300 binding or CREB transactivation
Mori et al., Cancer Res 2000 (HTLV-I Infections...) : Through the use of an electrophoretic mobility shift assay, we demonstrated that Tax induced NF-kappaB binding to both MCP-1 kappaB sites
Yi et al., Biochem Biophys Res Commun 2000 : Deletion analyses showed that the response-element resides within the promoter region of -69 bp and that an NF-kappaB binding site at -41 bp is involved in the Tax-activation of the FN promoter ... Overexpression of NF-kappaB enhanced the Tax-activation of the FN promoter
Li et al., AIDS Res Hum Retroviruses 2000 (Cell Transformation, Neoplastic...) : In contrast to the transient activation of the NF-kappaB pathway seen in response to cytokines, Tax results in constitutive nuclear levels of NF-kappaB
Sun et al., AIDS Res Hum Retroviruses 2000 : Tax activates NF-kappaB by stimulating the activity of the I-kappaB kinase (IKK), which in turn leads to phosphorylation and degradation of the NF-kappaB inhibitor I-kappaBalpha
Pise-Masison et al., AIDS Res Hum Retroviruses 2000 : We further demonstrate the importance of Tax activation of NF-kappaB in p53 inhibition, using p65 knockout ( KO ) mouse embryo fibroblasts ( MEFs )
Mariner et al., J Immunol 2001 (Leukemia-Lymphoma, Adult T-Cell) : Furthermore, using promoter deletion constructs and gel shift analysis, we defined a functional NF-kappaB binding motif in the human IL-15Ralpha promoter, suggesting that Tax activation of IL-15Ralpha is due , in part, to the induction of NF-kappaB
Ng et al., Oncogene 2001 : Genome-wide expression changes induced by HTLV-1 Tax : evidence for MLK-3 mixed lineage kinase involvement in Tax mediated NF-kappaB activation ... Functionally, we provide evidence that one of these genes, the mixed-lineage kinase MLK-3, is involved in Tax mediated NF-kappa-B signaling
Nicot et al., Mol Cell Biol 2001 : In addition, inhibition of Tax mediated NF-kappaB activation by coexpression of IkappaBalpha restored c-Myb transcription, and Tax was unable to block c-Myb transcription in a NEMO knockout cell line
Zetoune et al., Cytokine 2001 : Similarly, the NF-kappa B inducing activity of TAX , an activator of the I kappa B kinase complex, is also abrogated by A20
Endo et al., J Virol 2002 (Cell Transformation, Viral) : Activation of cellular genes by Tax1 through transcription factor NF-kappa B is reportedly essential for the transformation of Rat-1 cells
Huang et al., FEBS Lett 2002 : Human T-cell leukemia virus type 1 oncoprotein Tax activates NF-kappaB through direct binding to IKK-gamma, the regulatory component of the IkappaB kinase complex ... Taken together, our findings suggest a new model of Tax activation of NF-kappaB , in which Tax interacts with IKK-gamma to stimulate its oligomerization
Nasr et al., Blood 2003 (Leukemia-Lymphoma, Adult T-Cell) : The As/IFN combination reduced Tax expression and, accordingly, reversed the Tax induced constitutive nuclear factor kappaB (NF-kappaB) activation
Carter et al., J Biol Chem 2003 : Although its precise mechanism of action remains unknown, IKKgamma is phosphorylated in concert with the induction of NF-kappaB by the viral oncoprotein Tax and the proinflammatory cytokine tumor necrosis factor alpha (TNF)
Schreck et al., J Virol 1992 : In this study, we used the antioxidant pyrrolidine dithiocarbamate ( PDTC ) to investigate whether the activation of NF-kappa B by the viral transactivator Tax from human T-cell leukemia virus type I also depends on the production of reactive oxygen intermediates ... The Tax induced activation of the DNA binding activity of NF-kappa B in Jurkat T cells was potently suppressed by micromolar concentrations of PDTC
Iha et al., Oncogene 2003 : Second, using NEMO knockout mouse fibroblasts and 10 NEMO mutants, we found that different regions function in trans either to complement or to inhibit dominantly TNFalpha, IL-1beta, or Tax activation of NF-kappaB ... For instance, NEMO ( 1-245 amino acids ) supported Tax mediated NF-kappaB activation, but did not serve TNFalpha- or IL-1beta signaling
O'Mahony et al., J Biol Chem 2004 (Cell Transformation, Viral) : However, NF-kappaB induced by Tax in these IKK1 ( -/- ) cells was functionally impaired ... Furthermore, reconstitution of IKK1 ( -/- ) cells with kinase-proficient ( but not kinase-deficient ) forms of IKK1 restored the Tax induction of full NF-kappaB transactivation ... Together, these findings highlight distinct roles for the IKK1 and IKK2 kinases in the activation of NF-kappaB in response to HTLV-1 Tax
Mori et al., J Virol 2004 (Disease Models, Animal...) : Although the viral protein Tax is an activator of NF-kappaB and AP-1, FR901228 induced apoptosis was not associated with reduced expression of Tax
Trevisan et al., Exp Cell Res 2004 : As Tax can enhance the transcriptional activity of nuclear factor NF-kB and cAMP-responsive element binding protein/activating transcription factor-1 ( CREB/ATF-1 ), we investigated the relevance of these routes in the anti-apoptotic effects of Tax
Akita et al., Virology 2005 : Previously, we reported that p21WAF1 stimulated Tax dependent NF-kappaB activation which influences a variety of cellular processes, including proliferation, differentiation, and apoptosis ... In HTLV-1 infected cells, Tax is primarily involved in the constitutive activation of NF-kappaB signaling ... Here, we demonstrate that p21WAF1 affects Tax dependent NF-kappaB signaling by inducing p100/52, an NF-kappaB related protein
Harhaj et al., Virology 2005 : CD40 ligation strongly synergized with Tax to activate NF-kappaB, suggesting that CD40 signals may costimulate Tax mediated NF-kappaB activation, particularly when Tax is expressed at low levels
Miyazato et al., J Virol 2005 : Evidence for NF-kappaB- and CBP independent repression of p53 's transcriptional activity by human T-cell leukemia virus type 1 Tax in mouse embryo and primary human fibroblasts ... To address this issue, we have investigated Tax 's effect on p53 's transcriptional activation in IkappaB-kinase-deficient mouse embryonic fibroblasts ( MEFs ) ; some of which are entirely silent for Tax induced NF-kappaB activity
Harhaj et al., IUBMB Life 2005 (Leukemia-Lymphoma, Adult T-Cell) : Tax activation of NF-kappaB is critical for the immortalization and survival of HTLV-I infected T cells
Kwon et al., J Biol Chem 2005 (Inflammation...) : These findings suggest that Tax mediated activation of NF-kappaB plays a key role in the development of this aggressive skin disease that shares several features in common with the skin disease occurring during the preleukemic stage in HTLV-I infected patients
Tomita et al., Int J Cancer 2006 (Leukemia, T-Cell...) : Curcumin also inhibited Tax induced NF-kappaB transcriptional activity
Sun et al., Oncogene 2005 (Leukemia-Lymphoma, Adult T-Cell) : Whereas Tax plays a primary role in HTLV-I mediated NF-kappaB activation, recent studies reveal that the IKK/NF-kappaB signaling pathway is also activated in freshly isolated adult T-cell leukemia ( ATL ) cells that often lack detectable Tax expression
Peloponese et al., J Biol Chem 2006 (Cell Transformation, Viral) : Most of the existing data point to Tax activation of NF-kappaB as important for cellular proliferation and transformation
Babu et al., J Biol Chem 2006 : Finally, Tpl2/Cot participates in the activation of NF-kappaB by Tax
Hai et al., J Virol 2006 : Because IKKgamma-Delta protein is lacking a critical coiled-coil domain important in protein-protein interactions, we sought to determine its signaling properties by examining its ability to self associate, couple to activators of the canonical pathway, and mediate human T-cell leukemia virus type 1 ( HTLV-1 ) Tax induced NF-kappaB activity
Arima et al., J Virol 1991 : Tax induction of the nuclear expression of c-Rel and NF-kappa B p50 is regulated, at least in part, at a pretranslational level involving increases in c-rel and NF-kappa B p105 mRNA expression
Hong et al., J Biol Chem 2007 : Interestingly, peptides spanning CCR2 and/or LZ disrupt IKKgamma-Tax and IKKgamma-PP2A interactions and potently inhibit NF-kappaB activation by Tax and tumor necrosis factor-alpha
Wu et al., EMBO Rep 2007 : Tax activates NF-kappaB by stimulating the activity of IkappaB kinase (IKK), but the underlying mechanism remains elusive
Lindholm et al., J Virol 1992 : Tax1 induction of NF-kappa B occurred in the presence of cycloheximide, and Tax1 stimulation did not result in increased levels of NF-kappa B or c-rel RNA
Gohda et al., Biochem Biophys Res Commun 2007 : HTLV-1 Tax induced NFkappaB activation is independent of Lys-63-linked-type polyubiquitination ... Human T-cell leukemia virus type 1 ( HTLV-1 ) Tax induced activation of nuclear factor-kappaB (NFkappaB) is thought to play a critical role in T-cell transformation and onset of adult T-cell leukemia ... However, the molecular mechanism of the Tax induced NFkappaB activation remains unknown ... However, TAK1 is dispensable for Tax induced NFkappaB activation, and deubiquitination of the K63 polyubiquitin chain failed to block Tax induced NFkappaB activation ... In addition, silencing of other MAP3Ks, including MEKK1, MEKK3, NIK, and TPL-2, did not affect Tax induced NFkappaB activation ... These results strongly suggest that unlike cytokine signaling, Tax induced NFkappaB activation does not involve K63 polyubiquitination mediated MAP3K activation
Fontan et al., FEBS J 2007 : In response to constitutive NF-kappaB stimulation by Tax , we observed NEMO recruitment and oligomerization to a shifted high-molecular-mass complex of 440 kDa which displayed increased IKK activity
Merling et al., Retrovirology 2007 : HTLV-1 Tax is a potent activator of viral transcription and NF-kappaB
Mizobe et al., Exp Hematol 2007 (Cell Transformation, Viral) : HTLV-I Tax enhanced TLR expression and synergistically activated NF-kappaB with wild-type MyD88
Shembade et al., J Virol 2007 : Ubiquitination of the human T-cell leukemia virus 1 Tax oncoprotein provides an important regulatory mechanism that promotes the Tax mediated activation of NF-kappaB ... Tax interacts with Ubc13, and small interfering RNA mediated knockdown of Ubc13 expression abrogates Tax ubiquitination and the activation of NF-kappaB ... Mouse fibroblasts lacking Ubc13 exhibit impaired Tax activation of NF-kappaB despite normal tumor necrosis factor- and interleukin-1 mediated NF-kappaB activation ... Collectively, our results reveal that Ubc13 is essential for Tax ubiquitination, its interaction with NEMO, and Tax mediated NF-kappaB activation
Yu et al., Biochem Biophys Res Commun 2008 : We found that TAB2 physically interacts with Tax and augments Tax induced NF-kappaB activity
Smith et al., J Clin Invest 1991 (Cell Transformation, Neoplastic...) : Tax also induces the nuclear expression of the NF-kappa B family of rel oncogene related enhancer binding proteins
Azran-Shaish et al., J Mol Med (Berl) 2008 (Leukemia, T-Cell) : On this ground, the present study suggests that such conditions may enhance the risk for ATL and TSP-HAM in HTLV-1 carriers by increasing the Tax induced NF-kappaB activation
Kim et al., J Virol 2008 : An intronic NF-kappaB binding site within the Bcl3 gene served as the primary target of Tax induced NF-kappaB activation
Zhao et al., Blood 2009 : The activation of NF-kappaB by Tax has been reported to play a crucial role in HTLV-1 induced transformation ... Selective suppression of the classical NF-kappaB pathway by HBZ renders the alternative NF-kappaB pathway predominant after activation of NF-kappaB by Tax or other stimuli, which might be critical for oncogenesis
Huang et al., J Biol Chem 2009 (Cell Transformation, Viral...) : Retroviral Tax proteins from human T cell leukemia virus type 1 and type 2 ( HTLV-1 and -2 ) are capable of activating IKK, yet only HTLV-1 infection causes T cell leukemia, which correlates with persistent activation of NF-kappaB induced by Tax1
Peloponese et al., J Virol 2009 : Tax activation of NF-kappaB is important for the proliferation and transformation of virus infected cells ... We show here that prolyl isomerase Pin1 is over expressed in HTLV-1 cell lines ; Pin1 binds Tax and regulates Tax induced NF-kappaB activation
Tomita et al., Int J Cancer 2009 (Leukemia-Lymphoma, Adult T-Cell) : Transfection of Aurora A expression plasmid enhanced Tax induced nuclear factor-kappaB (NF-kappaB) reporter activity
Journo et al., PLoS Pathog 2009 : Tax1 activation of NF-kappaB occurs predominantly in the cytoplasm, where Tax1 binds NF-kappaB Essential Modulator ( NEMO/IKKgamma ) and triggers the activation of IkappaB kinases ... Several independent studies have shown that Tax1 mediated NF-kappaB activation is dependent on Tax1 ubiquitination ... In addition, we observe that NRP increases the ubiquitination of Tax1 along with Tax1 dependent NF-kappaB signaling
Ruben et al., New Biol 1990 (Burkitt Lymphoma) : Transient short-term expression of the Tax protein of human T-cell leukemia virus type-I ( HTLV-I ) leads to activation of the pleiotropic transcription factor NF-kappa B
Shoji et al., Retrovirology 2009 (Cell Transformation, Viral...) : Using a series of Tax1 chimeric proteins with Tax2, we found that amino acids 225-232 of Tax1 , the Tax1 ( 225-232 ) region, was essential for the activation of NF-kappa B2 as well as for the high transforming activity
Tanji et al., Blood 2010 : Twist augmented Tax mediated HTLV-1 LTR and NF-kappaB activation
Lindholm et al., New Biol 1990 (Cell Transformation, Viral) : Tax1 activation of NF-kappa B was not sensitive to either staurosporin or prolonged stimulation with the phorbol ester 12-O-tetradecanoylphorbol-13-acetate, suggesting that Tax1 dependent NF-kappa B activation did not require the protein kinase C pathway ... Purified Tax1 did not directly increase NF-kappa B binding activity in 70Z/3 cytoplasmic extracts, suggesting that NF-kappa B induction may require cellular factors
Smith et al., Genes Dev 1990 : In contrast, Tax transactivation of the interleukin-2 receptor-alpha gene ( IL-2R alpha ) and LTR of the type 1 human immunodeficiency virus ( HIV-1 ) involves the induced nuclear expression of NF-kappa B
Ruben et al., New Biol 1989 : Activation of NF-kappa B by the HTLV-I trans-activator protein Tax requires an additional factor present in lymphoid cells ... We show that activation of NF-kappa B by Tax is an indirect process that requires prior activation of a preexistent factor that is present in lymphoid cells
Maggirwar et al., Oncogene 1995 : Activation of NF-kappa B/Rel by Tax involves degradation of I kappa B alpha and is blocked by a proteasome inhibitor ... In the present study, we demonstrate that Tax mediated activation of NF-kappa B/Rel can be inhibited by a proteasome inhibitor, suggesting the involvement of proteolytic reactions in this Tax-specific activation pathway ... Together, these studies suggest that Tax activation of NF-kappa B/Rel may involve induction of phosphorylation and subsequent proteasome mediated degradation of the inhibitor I kappa B alpha
Suzuki et al., Oncogene 1995 : These findings suggest that Tax induces dissociation of and/or inhibits the formation of NF-kappa B/I kappa B-alpha complexes, resulting in release of NF-kappa B and destabilization of I kappa B-alpha ... These Tax effects counteract the negative feedback control of NF-kappa B by I kappa B-alpha and contribute to constitutive activation of NF-kappa B in Tax transfected and HTLV-1 infected cells
Kanno et al., Proc Natl Acad Sci U S A 1994 : Human T-cell leukemia virus type I Tax-protein mediated activation of NF-kappa B from p100 ( NF-kappa B2 ) -inhibited cytoplasmic reservoirs ... Induction of these genes is mediated, at least in part, through Tax dependent posttranslational activation of NF-kappa B , typically heterodimers of p50 ( NF-kappa B1 ) and p65 ( RelA ) ... The results demonstrate a mechanism by which Tax may activate NF-kappa B in T cells
Murakami et al., Virology 1995 : HTLV-1 Tax enhances NF-kappa B2 expression and binds to the products p52 and p100, but does not suppress the inhibitory function of p100 ... Here, we report that Tax enhances expression of NF-kappa B2 at the mRNA level and proteins ; the effect was more apparent on the p52 expression than on its precursor p100, suggesting post-translational regulation
Kanno et al., Mol Cell Biol 1994 : However, neither underlying mechanisms nor kinetics of the Tax mediated activation of NF-kappa B are understood
Sun et al., Mol Cell Biol 1994 : Human T-cell leukemia virus type I Tax activation of NF-kappa B/Rel involves phosphorylation and degradation of I kappa B alpha and RelA ( p65 ) -mediated induction of the c-rel gene ... HTLV-I Tax expression leads to the constitutive nuclear expression of biologically active NF-kappa B and c-Rel complexes ; however, the biochemical mechanism ( s ) underlying this response remains poorly understood ... In this study, we demonstrate that Tax stimulated nuclear expression of NF-kappa B in both HTLV-I infected and Tax transfected human T cells is associated with the phosphorylation and rapid proteolytic degradation of I kappa B alpha ... However, the pathologic action HTLV-I Tax leads to the deregulated and sustained nuclear expression of both NF-kappa B and c-Rel, a response that may contribute to HTLV-I induced T-cell transformation
Muñoz et al., J Virol 1994 : Tax induces nuclear translocation of NF-kappa B through dissociation of cytoplasmic complexes containing p105 or p100 but does not induce degradation of I kappa B alpha/MAD3 ... These results suggest that Tax activates NF-kappa B essentially through the p105/p100 retention pathway
Lacoste et al., Leukemia 1994 : NF-kappa B proteins differentially trans activated the HIV-1 enhancer-CAT reporter ; co-expression of Tax abrogated the inhibitory effect of I kappa B alpha and a trans-dominant negative mutant of p65 ( p65 delta ), indicating that Tax was a trans-dominant activator of NF-kappa B-regulated genes
Béraud et al., Mol Cell Biol 1994 (Leukemia, T-Cell) : Human T-cell leukemia virus type I Tax associates with and is negatively regulated by the NF-kappa B2 p100 gene product : implications for viral latency
Watanabe et al., Oncogene 1993 : HTLV-I encoded Tax in association with NF-kappa B precursor p105 enhances nuclear localization of NF-kappa B p50 and p65 in transfected cells
Munoz et al., Immunobiology 1995 : These results suggest that Tax activates NF-kappa B essentially through the p105/p100-retention pathway
Lemasson et al., J Immunol 1996 : The Ig CDR3-like region-specific mAb, 13B8-2, blocked HIV-1 production in CD4-positive/p56Ick negative HTLV-I producing MT2 cells superinfected by HIV-1Lai, but had no effect on HTLV-I production, although it did inhibit Tax induced NF-kappa B translocation
Yamaoka et al., EMBO J 1996 (Cell Transformation, Neoplastic) : Stable expression of Tax competent for transformation caused enhanced DNA binding of NF-kappa B in rat fibroblasts ... We also demonstrate that stable co-expression of the NFKB2 precursor, known as a member of the I kappa B proteins, with wild-type Tax blocked transformation as well as eliminated aberrant NF-kappaB activation by Tax without interference with the HTLV-I LTR mediated trans-activation
Lindholm et al., J Virol 1996 : Human T-cell lymphotropic virus type 1 Tax1 activation of NF-kappa B : involvement of the protein kinase C pathway ... Human T-cell lymphotropic virus type 1 Tax1 induces the activation and nuclear localization of the cellular transcription factor, NF-kappa B
Béraud et al., J Acquir Immune Defic Syndr Hum Retrovirol 1996 (Cell Transformation, Viral...) : The mechanisms by which Tax activates NF-kappa B remain unclear, and findings presented in the literature are often controversial
Kitajima et al., Rinsho Byori 1997 (Arthritis...) : We think activation of NF-kappa B by Tax is important for tumor progression
Inoue et al., Jpn J Cancer Res 1998 (Leukemia, T-Cell) : These findings in vivo are strikingly different from those in HTLV-1 infected T cell lines in vitro, in which Tax is responsible for NF-kappaB activation
Bex et al., Mol Cell Biol 1998 (Cell Transformation, Viral) : These studies are consistent with a model in which activation of either the NF-kappaB or the ATF/CREB pathway by specific Tax mutants is mediated by distinct interactions with related coactivator proteins
Ohtani et al., J Biol Chem 1998 : Both NF-kappaB-like elements were able to bind to NF-kappaB or its related factor ( s ) in a Tax dependent manner
Yin et al., Cell 1998 : NF-kappaB , a key regulator of the cellular inflammatory and immune response, is activated by the HTLV-I transforming and transactivating protein Tax
Chu et al., J Biol Chem 1998 (HTLV-I Infections) : Moreover, point mutations in Tax that ablate its IKK binding function also prevent Tax mediated activation of IKK and NF-kappaB
Nicot et al., J Virol 1998 : Cytoplasmic forms of human T-cell leukemia virus type 1 Tax induce NF-kappaB activation ... In contrast, they activated NF-kappaB reporters, suggesting that activation of NF-kappaB by Tax occurs in the cytoplasm
Uhlik et al., J Biol Chem 1998 : Consistently, inactive forms of either IKKs or NIK attenuate Tax mediated NF-kappaB activation ... Therefore, Tax activates NF-kappaB by targeting cellular signaling molecules, including both IKKs and NIK
Geleziunas et al., Mol Cell Biol 1998 (Cell Transformation, Viral...) : Human T-cell leukemia virus type 1 Tax induction of NF-kappaB involves activation of the IkappaB kinase alpha (IKKalpha) and IKKbeta cellular kinases ... Similarly, a kinase-deficient mutant of NIK ( NF-kappaB inducing kinase ), which represents an upstream kinase in the TNF-alpha and IL-1 signaling pathways leading to IKKalpha and IKKbeta activation, blocks Tax induction of NF-kappaB ... The pathological alteration of this cytokine pathway leading to NF-kappaB activation by Tax may play a central role in HTLV-1 mediated transformation of human T cells, clinically manifested as the adult T-cell leukemia ... However, plasma membrane-proximal elements in these proinflammatory cytokine pathways are apparently not involved since dominant negative mutants of the TRAF2 and TRAF6 adaptors, which effectively block signaling through the cytoplasmic tails of the TNF-alpha and IL-1 receptors, respectively, do not inhibit Tax induction of NF-kappaB
Los et al., J Immunol 1998 : Hormone induced Tax activation induces a long lasting activation of NF-kappaB , which is a major target of reactive oxygen intermediates