- Open Access
Specific TATAA and bZIP requirements suggest that HTLV-I Tax has transcriptional activity subsequent to the assembly of an initiation complex
© Ching et al; licensee BioMed Central Ltd. 2004
- Received: 27 May 2004
- Accepted: 30 July 2004
- Published: 30 July 2004
Human T-cell leukemia virus type I (HTLV-I) Tax protein is a transcriptional regulator of viral and cellular genes. In this study we have examined in detail the determinants for Tax-mediated transcriptional activation.
Whereas previously the LTR enhancer elements were thought to be the sole Tax-targets, herein, we find that the core HTLV-I TATAA motif also provides specific responsiveness not seen with either the SV40 or the E1b TATAA boxes. When enhancer elements which can mediate Tax-responsiveness were compared, the authentic HTLV-I 21-bp repeats were found to be the most effective. Related bZIP factors such as CREB, ATF4, c-Jun and LZIP are often thought to recognize the 21-bp repeats equivalently. However, amongst bZIP factors, we found that CREB, by far, is preferred by Tax for activation. When LTR transcription was reconstituted by substituting either κB or serum response elements in place of the 21-bp repeats, Tax activated these surrogate motifs using surfaces which are different from that utilized for CREB interaction. Finally, we employed artificial recruitment of TATA-binding protein to the HTLV-I promoter in "bypass" experiments to show for the first time that Tax has transcriptional activity subsequent to the assembly of an initiation complex at the promoter.
Optimal activation of the HTLV-I LTR by Tax specifically requires the core HTLV-I TATAA promoter, CREB and the 21-bp repeats. In addition, we also provide the first evidence for transcriptional activity of Tax after the recruitment of TATA-binding protein to the promoter.
- Long Terminal Repeat
- Core Promoter
- Basal Transcription Factor
- Serum Response Element
- Basal Transcription Machinery
In eukaryotes, transcription by RNA polymerase II requires the orderly recruitment of basal transcription factors and activators to the core promoter and enhancers, respectively [1, 2]. The core promoter contains the transcription initiation site, and it provides the docking sites for the basal transcription factors that nucleate the assembly of a functional preinitiation complex (PIC). The TATA box is one of four major core promoter elements, and it is specifically recognized by the TATA-binding protein (TBP), a subunit of the basal transcription factor TFIID which also contains at least 14 TBP-associated factors (TAFs). On the other hand, enhancers are bound by sequence-specific transcriptional activators that are thought to promote PIC assembly through interactions with components of the basal transcription machinery.
Human T-cell leukemia virus type I (HTLV-I) Tax protein is a unique transcriptional regulator . Tax can modulate the HTLV-I long terminal repeats (LTR), heterologous viral promoters, and a variety of cellular genes. In most context, Tax acts as a potent transcriptional activator through Tax-responsive DNA elements that are recognized by cellular transcription factors CREB, NFκB and serum response factor (SRF) [4–6]. For activation of the HTLV-I LTR, Tax targets three imperfectly conserved 21-bp direct repeats flanked by GC-rich sequences. In this scenario, Tax forms a ternary complex with CREB and the 21-bp repeat through physical interaction with CREB and direct contact with the flanking GC-rich sequences [7–9]. Tax-induced activation of other promoters is thought to be mediated through protein-protein interactions. Thus, Tax is a pleiotropic transcriptional activator that targets multiple enhancer elements through multiple cellular transcription factors.
To date, the molecular mechanisms for Tax trans-activation have been well studied. Due to its pleiotropic activities, there are likely nuances to Tax's activity which remain unrevealed. Currently, we understand Tax to harbor a minimal activation domain , to interact with basal transcription factors such as TBP , to form a homo-dimer [12–14], and to stimulate the dimerization of cellular regulatory factors such as CREB [15, 16] and IKK-γ . Moreover, we also know that Tax can directly engage transcriptional coactivators such as CREB-binding protein, p300 and P/CAF [18–20]. However, it remains unclear what is Tax's optimal preference for an enhancer – TATAA configuration. It has also been unaddressed whether Tax has a transcriptional activity after the formation of an initiation complex at the TATAA-box.
In mammalian cells, the artificial recruitment of TBP sufficiently activates transcription from some promoters [21–24]. It is understood that the structure of core promoter is one important determinant for this activation . On the other hand, DNA-tethered TBP can also work synergistically with selective natural activators such as human immunodeficiency virus type 1 (HIV-1) Tat protein [21–23] and cytomegalovirus IE2 protein . In this regard, it is not known whether TBP recruitment suffices for activation of HTLV-I minimal promoter. Nor is it clear whether Tax can cooperate with promoter-tethered TBP.
Here, we have constructed a series of chimeric enhancer-TATAA reporters to analyze the functional roles of these transcription elements in Tax-mediated activation. We observed that Tax activates the HTLV-I 21-bp repeats more potently than other enhancer elements. Analysis of ten mutants of Tax revealed that Tax utilizes different domains to target different cellular factors. We also found that multiple bZIP transcription factors including the newly-identified LZIP are involved in Tax activation of HTLV-I LTR. Finally, two other salient findings are that optimal Tax-responsiveness is specified by the HTLV-I-specific TATAA element, and that Tax synergizes with artificially recruited, DNA-tethered, TBP in a phase of transcription after the assembly of an initiation complex at the promoter.
Specific preference by Tax for only one enhancer element
Tax can activate transcription through 21-bp repeats, CRE, κB site or SRE [4–9]. However, a direct head-to-head comparison between the relative preferences of Tax for each of these elements is complicated by the context of additional DNA elements in the various promoters tested to date (i.e. the HTLV-I LTR versus the HIV-1 LTR versus the interleukin-2 promoter). To directly compare enhancer motifs, they should be placed in identical TATAA-context and tested in identical experimental settings. Towards this end, we constructed a series of six reporters to dissect the ordered preference of Tax for various enhancers.
When the reporters were tested in the presence of Tax, a different pattern emerged. Transcription from the 21-bp repeats was stimulated approximately 70-fold (Fig. 1D, lane 2 compared to lane 1) while that from the Sp1 site, not prototypically known to be responsive to Tax, was not activated significantly over the activity of the HTLV-I minimal promoter (Fig. 1D, lane 5 compared to lane 1). All other responses to Tax were markedly weaker than that seen from the 21-bp repeats. Hence, for all practical purposes, only a duplicated 21-bp repeat in the context of isolated placement upstream of an authentic HTLV-I minimal TATAA box could be regarded as significantly Tax-responsive in HeLa cells.
Multiple activation surfaces are configured in Tax
In Fig. 1D, the 21-bp repeats were activated by Tax >75 fold, while κB and SRE motifs were activated five and three fold, respectively. The low activation of the latter motifs, although comparatively less significant than that from the 21 bp elements, was real and reproducible. To further understand how Tax works, we wondered whether the different magnitudes of activation were due to quantitative or qualitative differences in protein-protein interaction. To address this question, we examined the separate responses of the three motifs to a battery of Tax mutants.
Based on percentage of activation relative to wild type Tax, we saw three patterns of mutant activity for 21 bp, κB and SRE (Fig. 3). Hence, the activation domain mutant Tax L320G  and the zinc finger mutant Tax H52Q  were defective in activating either 21-bp repeats or SRE, but were fully competent for κB (Fig. 3, lanes 4 and 10). By contrast, the N-terminal mutant Tax Δ3–6 and the point mutant Tax S258A activated 21-bp repeats and SRE well, but did not activate κB (Fig. 3, lanes 2 and 7). Additionally, mutants Tax Δ94–114, Tax S150A and Tax Δ337–353 were active on all three motifs (Fig. 3, lanes 5, 6 and 11), while neither Tax Δ2–58, Tax Δ 284–353 nor Tax L296G (Fig. 3, lanes 3, 8 and 9) activated any of the motifs. These non-identical patterns suggest that Tax may use different contact surfaces to target factors docked at the 21-bp repeats, κB or SRE. We note some similarity in the Tax mutant activity profiles for the 21-bp repeats and SRE suggesting that overlapping surfaces may be utilized.
Amongst bZIP factors, CREB is specifically preferred by Tax
Tax activates the HTLV-I LTR through the viral 21-bp repeats [7–9]. When compared to κB and SRE, the activation of 21-bp repeats by Tax is particularly effective (Fig. 1 and Fig. 2) and, based on mutant profiles (Fig. 3A), relies upon unique structural surfaces. Previously, it has been proposed that bZIP cellular transcription factors including CREB [9, 27, 28], ATF4 [29, 30] and c-Jun  play roles in Tax activation of 21-bp repeats. However, the relative contribution of these bZIP factors has not been compared directly in the same experimental setting. Furthermore, it remains undetermined whether additional newly identified bZIP proteins may also participate in Tax activation of 21-bp repeats.
To verify the specificity of dominant negative effects, we also tested the activities of dominant negative proteins on an NFκB-dependent reporter (Fig. 4B, blue columns). Noticeably, none of the dominant negative bZIP proteins had an effect on Tax activation of NFκB (Fig. 4B, groups 3–6 compared to group 2, blue columns). In contrast, the expression of IKKβ DN led to more than 50% suppression of NFκB activity (Fig. 4B, group 7, blue column). These results ruled out the possibility that A-CREB, A-ATF4, A-Fos and A-LZIP might non-specifically inhibit transcription.
Functional significance of the HTLV-I TATAA element to transcriptional activation by Tax
Evidence for Tax activity after assembly of an initiation complex
Artificial recruitment of TBP to some higher eukaryotic promoters bypasses transcriptional activation by a DNA-tethered activator [21–24]. When observed at such promoters, this finding is evident that those activators act mechanistically to enhance TBP recruitment to the TATAA box. For general transcriptional activation, additional events subsequent to TBP recruitment are also known to be functionally critical [21–23, 25]. To date, it remains unclear whether Tax works transcriptionally through a mechanism solely to recruit TBP or whether there are additional mechanistic implications after TBP is recruited to the TATAA-element.
Here, we have delineated functional requirements for both the TATAA promoter and the 21-bp enhancer elements in HTLV-I Tax mediated activation of the viral LTR. To date Tax has been considered solely to initiate transcription. Our study shows for the first time that Tax has a transcriptional role after assembly of an initiation complex at the promoter.
Preferential requirements for 21-bp repeats, CREB, and the HTLV-I TATAA box
HTLV-I is etiologically associated with adult T-cell leukemia [38, 39]. Expression of Tax leads to immortalization of T lymphocytes [40–42] and transformation of rat fibroblasts [43, 44]. Tax is a transcriptional activator that can interact pleiotropically with several different enhancers. In addition to the HTLV-I 21-bp repeats, κB and SRE elements can also mediate Tax activation [4–6]. Amongst these three enhancers, it is clear that the viral 21-bp repeats are the most highly responsive to Tax-activation (Fig. 1D). However, data elsewhere have raised questions as to the identity of the 21-bp binding bZIP factor which is best used to mediate Tax activation . In direct comparisons, we have used matched A-CREB, A-Jun, A-ATF4 and A-LZIP dominant negative mutants to ask which bZIP factor is most contributory to Tax activation. In our cell system, a novel bZIP factor called LZIP  can apparently participate in LTR transcription; however, for Tax activation CREB is preferred over ATF4 or c-Jun (Fig. 4).
Beyond the requirement for the 21-bp enhancer, our experiments revealed that the HTLV-I TATAA is also specifically preferred by Tax (Fig. 5 and Fig. 6). This finding is consistent with the general notion that core promoters can contribute specificity to transcriptional regulation . Indeed, core promoter preference by other cellular and viral activators such as Sp1, VP16 and Tat have been documented previously [45–47]. However, the reasons underlying core promoter preferences are poorly understood. TAFs have been suggested to be responsible for the core promoter selectivity of some activators [48–50]. In this vein, the interaction of Tax with TBP  and TBP-associated factors such as TAFII28  might provide mechanistic explanations.
Roles of Tax subsequent to TBP recruitment
A provocative notion which emerges from our study is that Tax can further activate a promoter at which TBP has already been artificially tethered (Fig. 7). Experiments in yeast and mammalian cells indicate that many genes can be activated through artificial recruitment of TBP and other components of the basal transcription machinery to their promoters [52, 53]. In yeast, artificial recruitment of TBP bypasses the effect of DNA-tethered activators whereas the activators fail to activate transcription when physically fused to components of the basal transcription machinery . This and other lines of evidence support the notion that activator-dependent recruitment of TBP and basal transcription machinery is a major mechanism for transcriptional activation in yeast cells [54, 55]. In contrast, artificial recruitment of TBP to mammalian promoters has not yet been extensively studied. Among the few promoters examined, some such as the ones from E1b and thymidine kinase genes can be fully activated by artificially recruited TBP, while others such as HIV-1 and c-fos promoters are stimulated weakly [21–25]. On the other hand, some activators such as VP16, E1A, Tat, E2F1 and IE2 work synergistically with artificially recruited TBP, while others such as Sp1 cannot further enhance the activity of DNA-tethered TBP [21, 22]. Thus, artificial recruitment of TBP might insufficiently activate transcription in mammalian cells and different activators might function at different steps with respect to TBP recruitment. Our results indicate that DNA-bound TBP can activate HTLV-I LTR only weakly, but its activity is further enhanced by Tax (Fig. 6). While such experimental results do not exclude that under physiological circumstances the primary function of Tax may be to enhance initiation complex formation (i.e. TBP-recruitment), they do indicate that Tax has an additional transcriptional activity that extends to phases after transcriptional initiation. Currently, we do not know whether this is at the step of promoter clearance, transcriptional elongation, or some other processes. However, we do believe that Tax should be added to the list of mammalian activators that can function at steps subsequent to TBP recruitment [21–25].
All the transcriptional assays in the present study were based on transiently transfected reporters. We noted that transiently transfected and stably integrated promoters might behave differently [24, 56]. Obviously, chromatin structure and copy numbers can account for significant differences [56, 57]. Future experiments are required to verify whether the observations established here also hold for stably integrated HTLV-I LTRs.
Chloramphenicol acetyltransferase (CAT) reporter plasmid pG5CAT was from Clontech. CAT plasmid pU3RCAT containing the HTLV-I LTR has been previously described . Other CAT plasmids were derived from pCAT-basic (Promega). For each construct, one copy of a minimal promoter and two copies of an enhancer were chemically synthesized and cloned into pCAT-basic. For example, pCRE-HTLV-CAT contains two copies of canonical CRE motif plus one copy of HTLV-I minimal promoter (Fig. 1A). Five copies of Gal4-binding sites as in pG5CAT were also inserted in some reporters. All constructs have the same spacing between the TATAA box and the CAT open reading frame (44 bp) or between the enhancer and the TATAA box (23 bp).
Sequences of canonical CRE, Sp1, AP1 and κB motifs in the reporter plasmids have been described [36, 58, 59]. HTLV-I 21-bp repeats and serum response element (SRE) in the plasmids were derived from the following synthetic oligonucleotides: 21-bp repeats, 5'-AGCTTAGGCC CTGACGTGTCCCCCTGGATCCTAGGCCCTGACGTGTCCCCCTA-3' and 5'-AGCTTAG GGGGACACGTCAGGGCCTAGGATCCAGGGGGACACGTCAGGGCCTA-3'; SRE, 5'-AGCTACCATATTAGGATCCATATTAGGT-3' and 5'-AGCTACCTAATATGGATCCTAATATGGT-3'. Sequences of the minimal promoter elements from HTLV-I, HIV-1, SV40 and adenoviral E1b have been described . The SV40 early promoter naturally used for expression of the viral T/t antigens was used.
Expression plasmids for wild type and mutant Tax have been described elsewhere [26, 61]. pIEX is a Tax expression vector driven by cytomegalovirus IE promoter. Tax mutants are indicated by the amino acid to be changed, the position of the residue, and the replacement amino acid (e.g. Tax S150A). Amino acids that were removed in mutants are indicated as in Tax Δ3–6. Expression vector pM for Gal4 DNA binding domain (Gal4DB; amino acids 1–147) was from Clontech. Tax, human TBP and the activation domain of VP16 fused to Gal4DB were designated Gal4-Tax, Gal4-TBP and Gal4-VP16, respectively. Expression plasmids for Gal4-Tax and Gal4-TBP have been described [10, 21]. Expression plasmid for Gal4-VP16 was from Clontech.
Expression plasmid pRSV-KCREB for the dominant-negative CREB protein KCREB  was kindly provided by Dr. Richard Goodman. Expression plasmids pCMV-ACREB and pCMV-AFOS for dominant-negative CREB and AP1 proteins A-CREB  and A-Fos  were gifts from Dr. Charles Vinson. Expression plasmid pCMV-TAM67 for dominant-negative c-Jun protein TAM67  was from Dr. Michael Birrer. Expression plasmids pCMV-AATF4 and pCMV-ALZIP for dominant-negative ATF4 and LZIP proteins A-ATF4 and A-LZIP were derived from pCMV500 provided by Dr. Charles Vinson [33, 37]. A-ATF4 contains 304–352 amino acids of human ATF4 and A-LZIP contains 175–223 amino acids of human LZIP. A-ATF4 and A-LZIP can specifically and dominantly inhibit the CRE-binding and CRE-activating activities of ATF4 and LZIP, respectively, in electrophoretic mobility shift assay and CAT reporter assay (data not shown). Expression plasmid for dominant-negative IKKβ (IKKβ DN) was a gift from Dr. Michael Karin .
HeLa cells were grown in Dulbecco's modified Eagle's medium supplemented with fetal calf serum and antibiotics, seeded at 5 × 105 cells/well into six-well culture plates and transfected using calcium phosphate method as described . Jurkat cells were cultured in RPMI 1640 medium and transfected by FUGENE 6 reagents (Roche). CAT activity was assayed as previously described . Briefly, transfected cells were harvested and lysed by freezing and thawing. Protein concentration of clarified lysates was determined by Bradford reagent (Bio-Rad). Equal amounts of lysates were mixed with 14C-labeled chloramphenicol (Amersham) and acetyl coenzyme A (Calbiochem) for CAT reaction. CAT activities were detected using thin-layer chromatography and quantified by phosphorimager (Molecular Dynamics). For transfection of cells, each well received the same dose of plasmids. The empty vector or pUC19 was added to compensate for the different amounts of plasmids when necessary.
We thank E.W.M. Cheng for technical assistance, R.H. Goodman, C. Vinson, M.J. Birrer and M. Karin for plasmids, and C.M. Wong and M.L. Yeung for critical reading of manuscript. D.-Y. J. is a Leukemia and Lymphoma Society Scholar. This work was supported by a Concern Foundation Research Grant, a Young Investigator Award from the National Natural Science Foundation of China (Project 30029001) and a matching grant from the University of Hong Kong.
- Lee TI, Young RA: Transcription of eukaryotic protein-coding genes. Annu Rev Genet. 2000, 34: 77-137. 10.1146/annurev.genet.34.1.77.View ArticlePubMedGoogle Scholar
- Smale ST, Kadonaga JT: The RNA polymerase II core promoter. Annu Rev Biochem. 2003, 72: 449-479. 10.1146/annurev.biochem.72.121801.161520.View ArticlePubMedGoogle Scholar
- Flint J, Shenk T: Viral transactivating proteins. Annu Rev Genet. 1997, 31: 177-212. 10.1146/annurev.genet.31.1.177.View ArticlePubMedGoogle Scholar
- Jeang KT, Boros I, Brady J, Radonovich M, Khoury G: Characterization of cellular factors that interact with the human T-cell leukemia virus type I p40x-responsive 21-base-pair sequence. J Virol. 1988, 62: 4499-4509.PubMed CentralPubMedGoogle Scholar
- Ballard DW, Bohnlein E, Lowenthal JW, Wano Y, Franza BR, Greene WC: HTLV-I tax induces cellular proteins that activate the κB element in the IL-2 receptor α gene. Science. 1988, 241: 1652-1655.View ArticlePubMedGoogle Scholar
- Fujii M, Sassone-Corsi P, Verma IM: c-fos promoter trans-activation by the tax1 protein of human T-cell leukemia virus type I. Proc Natl Acad Sci USA. 1988, 85: 8526-8530.PubMed CentralView ArticlePubMedGoogle Scholar
- Kimzey AL, Dynan WS: Specific regions of contact between human T-cell leukemia virus type I Tax protein and DNA identified by photocross-linking. J Biol Chem. 1998, 273: 13768-13775. 10.1074/jbc.273.22.13768.View ArticlePubMedGoogle Scholar
- Lenzmeier BA, Giebler HA, Nyborg JK: Human T-cell leukemia virus type 1 Tax requires direct access to DNA for recruitment of CREB binding protein to the viral promoter. Mol Cell Biol. 1998, 18: 721-731.PubMed CentralView ArticlePubMedGoogle Scholar
- Zhao LJ, Giam CZ: Interaction of the human T-cell lymphotrophic virus (HTLV) type I transcriptional activator Tax with cellular factors that bind specifically to the 21-base-pair repeats in the HTLV-I enhancer. Proc Natl Acad Sci USA. 1991, 88: 11445-11449.PubMed CentralView ArticlePubMedGoogle Scholar
- Semmes OJ, Jeang KT: Definition of a minimal activation domain in human T-cell leukemia virus type I Tax. J Virol. 1995, 69: 1827-1833.PubMed CentralPubMedGoogle Scholar
- Caron C, Rousset R, Béraud C, Moncollin V, Egly JM, Jalinot P: Functional and biochemical interaction of the HTLV-I Tax1 transactivator with TBP. EMBO J. 1993, 12: 4269-4278.PubMed CentralPubMedGoogle Scholar
- Tie F, Adya N, Greene WC, Giam CZ: Interaction of the human T-lymphotropic virus type 1 Tax dimer with CREB and the viral 21-base-pair repeat. J Virol. 1996, 70: 8368-8374.PubMed CentralPubMedGoogle Scholar
- Jin DY, Jeang KT: HTLV-I Tax self-association in optimal trans-activation function. Nucl Acids Res. 1997, 25: 379-388. 10.1093/nar/25.2.379.PubMed CentralView ArticlePubMedGoogle Scholar
- Basbous J, Bazarbachi A, Granier C, Devaux C, Mesnard JM: The central region of human T-Cell leukemia virus type 1 Tax protein contains distinct domains involved in subunit dimerization. J Virol. 2003, 77: 13028-13035. 10.1128/JVI.77.24.13028-13035.2003.PubMed CentralView ArticlePubMedGoogle Scholar
- Wagner S, Green MR: HTLV-1 Tax protein stimulation of DNA binding of bZIP proteins by enhancing dimerization. Science. 1993, 262: 395-399.View ArticlePubMedGoogle Scholar
- Baranger AM, Palmer CR, Hamm MK, Giebler HA, Brauweiler A, Nyborg JK, Schepartz A: Mechanism of DNA binding enhancement by the HTLV-I transactivator Tax. Nature. 1995, 376: 606-608. 10.1038/376606a0.View ArticlePubMedGoogle Scholar
- Huang GJ, Zhang ZQ, Jin DY: Stimulation of IKK-γ oligomerization by the T-cell leukemia virus oncoprotein Tax. FEBS Lett. 2002, 531: 494-498. 10.1016/S0014-5793(02)03590-1.View ArticlePubMedGoogle Scholar
- Kwok RP, Laurance ME, Lundblad JR, Goldman PS, Shih HM, Connor LM, Marriott SJ, Goodman RH: Control of cAMP-regulated enhancers by the viral transactivator Tax through CREB and the co-activator CBP. Nature. 1996, 380: 642-646. 10.1038/380642a0.View ArticlePubMedGoogle Scholar
- Jiang H, Lu H, Schiltz RL, Pise-Masison CA, Ogryzko VV, Nakatani Y, Brady JN: PCAF interacts with tax and stimulates tax transactivation in a histone acetyltransferase-independent manner. Mol Cell Biol. 1999, 19: 8136-8145.PubMed CentralView ArticlePubMedGoogle Scholar
- Harrod R, Kuo YL, Tang Y, Yao Y, Vassilev A, Nakatani Y, Giam CZ: 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. J Biol Chem. 2000, 275: 11852-11857. 10.1074/jbc.275.16.11852.View ArticlePubMedGoogle Scholar
- Xiao H, Lis JT, Jeang KT: Promoter activity of Tat at steps subsequent to TATA-binding protein recruitment. Mol Cell Biol. 1997, 17: 6898-6905.PubMed CentralView ArticlePubMedGoogle Scholar
- Majello B, Napolitano G, De Luca P, Lania L: Recruitment of human TBP selectively activates RNA polymerase II TATA-dependent promoters. J Biol Chem. 1998, 273: 16509-16516. 10.1074/jbc.273.26.16509.View ArticlePubMedGoogle Scholar
- Nevado J, Gaudreau L, Adam M, Ptashne M: Transcriptional activation by artificial recruitment in mammalian cells. Proc Natl Acad Sci USA. 1999, 96: 2674-2677. 10.1073/pnas.96.6.2674.PubMed CentralView ArticlePubMedGoogle Scholar
- Dorris DR, Struhl K: Artificial recruitment of TFIID, but not RNA polymerase II holoenzyme, activates transcription in mammalian cells. Mol Cell Biol. 2000, 20: 4350-4358. 10.1128/MCB.20.12.4350-4358.2000.PubMed CentralView ArticlePubMedGoogle Scholar
- Kim JM, Hong Y, Jeang KT, Kim S: Transactivation activity of the human cytomegalovirus IE2 protein occurs at steps subsequent to TATA box-binding protein recruitment. J Gen Virol. 2000, 81: 37-46.View ArticlePubMedGoogle Scholar
- Semmes OJ, Jeang KT: Mutational analysis of human T-cell leukemia virus type I Tax: regions necessary for function determined with 47 mutant proteins. J Virol. 1992, 66: 7183-7192.PubMed CentralPubMedGoogle Scholar
- Yoshimura T, Fujisawa JI, Yoshida M: Multiple cDNA clones encoding nuclear proteins that bind to the tax-dependent enhancer of HTLV-1: all contain a leucine zipper structure and basic amino acid domain. EMBO J. 1990, 9: 2537-2542.PubMed CentralPubMedGoogle Scholar
- Franklin AA, Kubik MF, Uittenbogaard MN, Brauweiler A, Utaisincharoen P, Matthews MA, Dynan WS, Hoeffler JP, Nyborg JK: Transactivation by the human T-cell leukemia virus Tax protein is mediated through enhanced binding of activating transcription factor-2 (ATF-2), ATF-2 response and cAMP element-binding protein (CREB). J Biol Chem. 1993, 268: 21225-21231.PubMedGoogle Scholar
- Reddy TR, Tang H, Li X, Wong-Staal F: Functional interaction of the HTLV-1 transactivator Tax with activating transcription factor-4 (ATF4). Oncogene. 1997, 14: 2785-2792. 10.1038/sj.onc.1201119.View ArticlePubMedGoogle Scholar
- Gachon F, Thebault S, Peleraux A, Devaux C, Mesnard JM: Molecular interactions involved in the transactivation of the human T-Cell leukemia virus type 1 promoter mediated by Tax and CREB-2 (ATF-4). Mol Cell Biol. 2000, 20: 3470-3481. 10.1128/MCB.20.10.3470-3481.2000.PubMed CentralView ArticlePubMedGoogle Scholar
- Jeang KT, Chiu R, Santos E, Kim SJ: Induction of the HTLV-I LTR by Jun occurs through the Tax-responsive 21-bp elements. Virology. 1991, 181: 218-227. 10.1016/0042-6822(91)90487-V.View ArticlePubMedGoogle Scholar
- Walton KM, Rehfuss RP, Chrivia JC, Lochner JE, Goodman RH: A dominant repressor of cyclic adenosine 3',5'-monophosphate (cAMP)-regulated enhancer-binding protein activity inhibits the cAMP-mediated induction of the somatostatin promoter in vivo. Mol Endocrinol. 1992, 6: 647-655. 10.1210/me.6.4.647.PubMedGoogle Scholar
- Ahn S, Olive M, Aggarwal S, Krylov D, Ginty D, Vinson C: A dominate-negative inhibitor of CREB reveals that it is a general mediator of stimulus-dependent transcription of c-fos. Mol Cell Biol. 1998, 18: 967-977.PubMed CentralView ArticlePubMedGoogle Scholar
- Olive M, Krylov D, Echlin DR, Gardner K, Taparowsky E, Vinson C: A dominant negative to activation protein-1 (AP1) that abolishes DNA binding and inhibits oncogenesis. J Biol Chem. 1997, 272: 8586-18594. 10.1074/jbc.272.30.18586.View ArticleGoogle Scholar
- Brown PH, Alani R, Preis LH, Birrer MJ: Suppression of oncogene-induced transformation by a deletion mutant of c-jun. Oncogene. 1993, 8: 877-886.PubMedGoogle Scholar
- Jin DY, Wang HL, Zhou Y, Chun ACS, Kibler KV, Hou YD, Kung H, Jeang KT: Hepatitis C virus core protein-induced loss of LZIP function correlates with cellular transformation. EMBO J. 2000, 19: 729-740. 10.1093/emboj/19.4.729.PubMed CentralView ArticlePubMedGoogle Scholar
- Vinson C, Myakishev M, Acharya A, Mir AA, Moll JR, Bonovich M: Classification of human B-ZIP proteins based on dimerization properties. Mol Cell Biol. 2002, 22: 6321-6335. 10.1128/MCB.22.18.6321-6335.2002.PubMed CentralView ArticlePubMedGoogle Scholar
- Matsuoka M: Human T cell leukemia virus type I and adult T-cell leukemia. Oncogene. 2003, 22: 5131-5140. 10.1038/sj.onc.1206551.View ArticlePubMedGoogle Scholar
- Azran I, Schavinsky-Khrapunsky Y, Aboud M: Role of Tax protein in human T-cell leukemia virus type-I leukemogenicity. Retrovirology. 2004,Google Scholar
- Grassmann R, Dengler C, Muller-Fleckenstein I, Fleckenstein B, McGuire K, Dokhelar MC, Sodroski JG, Haseltine WA: Transformation to continuous growth of primary human T lymphocytes by human T-cell leukemia virus type I X-region genes transduced by a herpesvirus saimiri vector. Proc Natl Acad Sci USA. 1989, 86: 3351-3355.PubMed CentralView ArticlePubMedGoogle Scholar
- Akagi T, Ono H, Shimotohno K: Characterization of T cells immortalized by Tax1 of human T-cell leukemia virus type 1. Blood. 1995, 86: 4243-4249.PubMedGoogle Scholar
- Kasai T, Jeang KT: Two discrete events, human T-cell leukemia virus type I Tax oncoprotein expression and a separate stress stimulus, are required for induction of apoptosis in T-cells. Retrovirology. 2004, 1: 7-10.1186/1742-4690-1-7.PubMed CentralView ArticlePubMedGoogle Scholar
- Tanaka A, Takahashi C, Yamaoka S, Nosaka T, Maki M, Hatanaka M: Oncogenic transformation by the tax gene of HTLV-I in vitro. Proc Natl Acad Sci USA. 1990, 87: 1071-1075.PubMed CentralView ArticlePubMedGoogle Scholar
- Gatza ML, Watt JC, Marriott SJ: Cellular transformation by the HTLV-I Tax protein, a jack-of-all-trades. Oncogene. 2003, 22: 5141-5149. 10.1038/sj.onc.1206549.View ArticlePubMedGoogle Scholar
- Emami KH, Navarre WW, Smale ST: Core promoter specificities of the Sp1 and VP16 transcriptional activation domains. Mol Cell Biol. 1995, 15: 5906-5916.PubMed CentralView ArticlePubMedGoogle Scholar
- Berkhout B, Jeang KT: Functional roles for the TATA promoter and enhances in basal and Tat-induced expression of the human immunodeficiency virus type 1 long terminal repeat. J Virol. 1992, 66: 139-149.PubMed CentralPubMedGoogle Scholar
- Southgate CD, Green MR: Delineating minimal protein domains and promoter elements for transcriptional activation by lentivirus Tat proteins. J Virol. 1995, 69: 2605-2610.PubMed CentralPubMedGoogle Scholar
- Green MR: TBP-associated factors (TAFIIs): Multiple selective transcriptional mediators in common complexes. Trends Biochem Sci. 2000, 25: 59-63. 10.1016/S0968-0004(99)01527-3.View ArticlePubMedGoogle Scholar
- Martel LS, Brown HJ, Berk AJ: Evidence that TAF-TATA box-binding protein interactions are required for activated transcription in mammalian cells. Mol Cell Biol. 2002, 22: 2788-2798. 10.1128/MCB.22.8.2788-2798.2002.PubMed CentralView ArticlePubMedGoogle Scholar
- Chen Z, Manley JL: Core promoter elements and TAFs contribute to the diversity of transcriptional activation in vertebrates. Mol Cell Biol. 2003, 23: 7350-7362. 10.1128/MCB.23.20.7350-7362.2003.PubMed CentralView ArticlePubMedGoogle Scholar
- Caron C, Mengus G, Dubrowskaya V, Roisin A, Davidson I, Jalinot P: Human TAFII28 interacts with the human T cell leukemia virus type I Tax transactivator and promotes its transcriptional activity. Proc Natl Acad Sci USA. 1997, 94: 3662-3667. 10.1073/pnas.94.8.3662.PubMed CentralView ArticlePubMedGoogle Scholar
- Xiao H, Friesen JD, Lis JT: Recruiting TATA-binding protein to a promoter: transcriptional activation without an upstream activator. Mol Cell Biol. 1995, 15: 5757-5761.PubMed CentralView ArticlePubMedGoogle Scholar
- Ptashne M, Gann A: Transcriptional activation by recruitment. Nature. 1997, 386: 569-577. 10.1038/386569a0.View ArticlePubMedGoogle Scholar
- Keaveney M, Struhl K: Activator-mediated recruitment of the RNA polymerase II machinery is the predominant mechanism for transcriptional activation in yeast. Mol Cell. 1998, 1: 917-924. 10.1016/S1097-2765(00)80091-X.View ArticlePubMedGoogle Scholar
- Li XY, Virbasius A, Zhu X, Green MR: Enhancement of TBP binding by activators and general transcription factors. Nature. 1999, 399: 605-609. 10.1038/21232.View ArticlePubMedGoogle Scholar
- Okada M, Jeang KT: Differential requirements for activation of integrated and transiently transfected human T-cell leukemia virus type 1 long terminal repeat. J Virol. 2002, 76: 12564-12573. 10.1128/JVI.76.24.12564-12573.2002.PubMed CentralView ArticlePubMedGoogle Scholar
- Ryan MP, Stafford GA, Yu L, Morse RH: Artificially recruited TATA-binding protein fails to remodel chromatin and does not activate three promoters that require chromatin remodeling. Mol Cell Biol. 2000, 20: 5847-5857. 10.1128/MCB.20.16.5847-5857.2000.PubMed CentralView ArticlePubMedGoogle Scholar
- Jin DY, Chae HZ, Rhee SG, Jeang KT: Regulatory role for a novel human thioredoxin peroxidase in NF-κB activation. J Biol Chem. 1997, 272: 30952-30961. 10.1074/jbc.272.49.30952.View ArticlePubMedGoogle Scholar
- Jin DY, Giordano V, Kibler KV, Nakano H, Jeang KT: Role of adaptor function in oncoprotein-mediated activation of NF-κB: HTLV-I Tax interacts directly with IκB kinase γ. J Biol Chem. 1999, 274: 17402-17405. 10.1074/jbc.274.25.17402.View ArticlePubMedGoogle Scholar
- Bucher P, Trifonov EN: Compilation and analysis of eukaryotic POL II promoter sequences. Nucl Acids Res. 1986, 14: 10009-10026.PubMed CentralView ArticlePubMedGoogle Scholar
- Chun ACS, Zhou Y, Wong CM, Kung H, Jeang KT, Jin DY: Coiled-coil motif as a structural basis for the interaction of HTLV type 1 Tax with cellular cofactors. AIDS Res Hum Retrov. 2000, 16: 1689-1694. 10.1089/08892220050193155.View ArticleGoogle Scholar
- Zandi E, Rothwarf DM, Delhase M, Hayakawa M, Karin M: The IκB kinase complex (IKK) contains two kinase subunits, IKKα and IKKβ, necessaryfor IκB phosphorylation and NF-κB activation. Cell. 1997, 91: 243-252. 10.1016/S0092-8674(00)80406-7.View ArticlePubMedGoogle Scholar
- Chun ACS, Jin DY: Transcriptional regulation of mitotic checkpoint gene MAD1 by p53. J Biol Chem. 2003, 278: 37439-37450. 10.1074/jbc.M307185200.View ArticlePubMedGoogle Scholar
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