1 Department of Biological Sciences, Korea Advanced Institute of Science and Technology, Daejeon 305-701, Korea
2 Department of Food and Nutrition, Hannam University, Daejeon 306-791, Korea
Correspondence
Joonho Choe
jchoe{at}mail.kaist.ac.kr
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ABSTRACT |
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Published ahead of print on 25 November 2002 as DOI 10.1099/vir.0.18699-0.
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INTRODUCTION |
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The most important step in the KSHV life cycle may be the switch from latency to lytic replication; virus lytic replication is critical for the development of KS (Boshoff et al., 1995; Miller et al., 1997
; Schulz et al., 1998
). In the latent phase, expression of a limited number of viral genes occurs and the genome is maintained in an episomal form. Lytic phase is characterized by a cascade of gene expression resulting in productive release of virions from infected cells. Lytic reactivation of KSHV can be induced artificially by phorbol esters such as 12-O-tetradecanoylphorbol-13-acetate (TPA) or n-butyrate, in a manner similar to EBV-infected B cell lines (Renne et al., 1996
). Upon chemical induction, KSHV produces immediate-early viral transcripts within 4 h. These transcripts encode viral transcriptional activator proteins, such as open reading frame 50 (ORF 50). From its expression pattern and function, ORF 50 appears to be the principal driver of the lytic cascade and functions as a switch gene in the disruption of latency (Lukac et al., 1998
; Sun et al., 1998
; Zhu et al., 1999
).
The KSHV ORF K8 gene encodes an early lytic protein that is activated by, and expressed after, KSHV ORF 50 protein (Lin et al., 1999; Sun et al., 1999
). Three forms of K8 protein result from alternative splicing and usage of different stop codons. The major form of K8 is a protein of 237 aa with a prototypic basic region-leucine zipper (bZIP) domain at the carboxyl terminus and it homodimerizes using this domain. An acidic domain between residues 6 and 47 (Zhu et al., 1999
) suggests that K8 (K-bZIP) may be a member of the bZIP family of transcription factors. This hypothesis is supported further by amino acid sequence analysis showing significant similarity between K8 and the EBV immediate-early gene product Zta (BZLF1, EB1, Z), a transactivator responsible for EBV replication and reactivation from latency to the lytic life cycle (Gruffat et al., 1999
; Lin et al., 1999
; Zhu et al., 1999
).
Recent data showed that K8 homodimerizes in the cytoplasm and is transported to the nucleus (Hwang et al., 2001; Portes-Sentis et al., 2001
). K8 interacts and co-localizes with CREB-binding protein (CBP) and has the capacity to modulate CBP-mediated transcription (Hwang et al., 2001
). K8 also represses the transcriptional activity of p53 (Park et al., 2000
). These data imply that K8 may be a nuclear protein involved in KSHV-driven transcription. K8 associates and co-localizes with the KSHV pseudo-replication compartment structure and with the promyelocytic leukaemia protein (PML) in PML oncogenic domains (PODs) (Wu et al., 2001
). It is known that p53 is sequestered in virus replication centres in the nuclei of cells infected with human cytomegalovirus (Fortunato & Spector, 1998
) and that K8 recruits p53 to the PODs (Katano et al., 2001
). PML is associated with virus replication (Adamson & Kenney, 2001
; Bell et al., 2000
), suggesting further that K8 plays a role in KSHV replication. Finally, K8 is phosphorylated by cyclin-dependent kinases (CDKs) and the phosphorylation state of K8 may link KSHV DNA replication to the cell cycle (Polson et al., 2001
).
In the present study, we show that K8 interacts with hSNF5, a component of the SWISNF chromatin-remodelling complex. Yeast two-hybrid screening showed that K8 binds to hSNF5 and further experiments showed this interaction requires aa 48183 of hSNF5 and 175 of K8. In mammalian BCBL-1 cells, which contain KSHV DNA, K8 co-immunoprecipitates with hSNF5. We found that K8 and mutant K8(1115) have transactivating properties and in yeast these required SNF5, the yeast homologue of hSNF5. We propose that K8 functions as a transcriptional activator and that this activity requires interaction with the cellular chromatin-remodelling factor hSNF5.
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METHODS |
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Plasmids.
Full-length K8 and its deletion mutants (together referred to as the K8 series) were cloned into the pcDNA3 plasmid (Invitrogen), as described previously (Hwang et al., 2001), to create the pcDNA3/K8 series. To construct hybrid expression vectors containing the LexA DNA-binding domain (DBD), we subcloned EcoRI/XhoI-digested fragments of the pcDNA3/K8 series into the EcoRIXhoI site of pLexA (Clontech). For Gal4DBD-fused expression vectors, EcoRIXhoI fragments of the pcDNA3/K8 series were subcloned into the EcoRISalI site of pM (Clontech), and EcoRIXbaI fragments of the pcDNA3/K8 series were subcloned into the EcoRIXbaI site of pcDNA3-Gal4 (Gal4DBD is inserted in pcDNA3). Glutathione S-transferase (GST)-fused mammalian expression vector pEBG/K8 was constructed by subcloning K8 products amplified by PCR from the pcDNA3/K8 series into the BamHINotI site of pEBG (a gift from J. Jung, Harvard Medical School, MA, USA). To construct amino-terminal, Flag-tagged vectors, we subcloned EcoRIXhoI fragments of the pcDNA3/K8 series into the EcoRIXhoI site of pME18S [an SR
promoter-based eukaryotic expression vector (Shiio et al., 1992
)]. To construct green fluorescent protein (GFP)-tagged K8, the K8 PCR product from pcDNA3/K8 was subcloned into the EcoRIXhoI site of pEGFP-C1 (Clontech) to create pEGFP/K8.
To construct the Flag-tagged and prokaryotic GST-fused hSNF5 expression vector, EcoRI/XhoI-digested fragments of the hSNF5 PCR product from pcDNA-HA/hSNF5 were subcloned into the EcoRIXhoI sites of pME18S and pGEX4T-1 (Amersham Pharmacia), respectively. pEBG/hSNF5 was constructed by subcloning BamHINotI fragments of pGEX4T-1/hSNF5 into the BamHINotI site of pEBG.
Yeast two-hybrid assay.
The yeast two-hybrid assay was performed using the MATCHMAKER LexA Two-Hybrid system, according to the manufacturer's instructions (Clontech). The yeast strain EGY48 (MAT his3 trp1 ura3 6lexAop-LEU2) harbouring pLexA/K8(175) and p8op-lacZ was transformed (by the lithium acetate method) with a B cell cDNA fusion library (20 µg) cloned into the activation-domain vector pB42AD. Transformants were selected by culture on synthetic minimum medium (-His/-Leu/-Trp/-Ura) with galactose for 3 days and were then patched onto fresh synthetic minimum medium (-His/-Trp/-Ura) with glucose. Positive clones were tested for galactose-dependent
-galactosidase activity.
-Galactosidase expression in yeast was assayed as described previously (Guarante, 1983
).
Transfection and reporter assay.
293T cells were transfected using the calcium phosphate precipitation method (Graham & van der Eb, 1973) and 48 h later were washed with PBS and lysed (Promega Cell Culture Lysis reagent). Reporter plasmid luciferase activity was measured according to the manufacturer's instructions (Promega) and was calculated after normalizing to
-galactosidase activity from a co-transfected Rous sarcoma virus (RSV)-
-Gal control plasmid. All experiments were performed in triplicate and the expression of each plasmid was verified by Western blot assay. DNA masses used for transfections were 1 µg reporter plasmid, 100 ng RSV-
-Gal control plasmid and 1 µg expression plasmid. The total amount of expression vector was kept constant.
Immunoblot analysis.
Transfected 293T cells or transformed yeast cells were washed with PBS and lysed with 6xSDS sample buffer [0·28 M Tris/HCl, pH 6·8, 30 % (v/v) glycerol, 1 % (w/v) SDS, 0·5M DTT and 0·0012 % (w/v) bromophenol blue]. Cell lysates were subjected to SDS-PAGE and electroblotted onto nitrocellulose membranes. After blocking with 5 % skimmed milk, membranes were incubated with appropriate first antibody (-Gal4,
-Flag,
-GST,
-K8,
-hSNF5,
-LexA or
-
-Actin) at a concentration of 100 ng ml-1 for 1 h, then appropriate secondary antibody (anti-mouse or anti-rabbit) conjugated with alkaline phosphatase for 1 h at a concentration of 50 ng ml-1. All procedures were performed at room temperature and membranes were washed with PBST (0·1 % Tween 20 in PBS) between each step. The reaction product was visualized using Enhanced Chemiluminescence (ECL) reagent, according to the manufacturer's instructions (Amersham Pharmacia).
Immunoprecipitation.
Transfected 293T or TPA-stimulated BCBL-1 cells were washed with PBS and lysed 48 h after transfection or chemical induction. Cells were harvested and lysed in binding buffer [20 mM HEPES (pH 7·4), 100 mM NaCl, 1 % Triton X-100, 0·5 % NP-40 and protease inhibitors], mixed for 1 h at 4 °C and centrifuged to remove cell debris. After pre-clearing by absorption to protein G- and A-Sepharose (Santa Cruz Biotechnology), lysates were incubated with antibodies against Flag (-Flag), GST (
-GST), K8 (
-K8) or hSNF5 (
-hSNF5) at a concentration of 1 µg ml-1 and 4 °C for 1 h. Then, protein G- and A-Sepharose was added and the reaction mixture was incubated at 4 °C for overnight. The beads were washed four times and immunoprecipitated proteins were separated using SDS-PAGE. Proteins were transferred to a nitrocellulose membrane which was subjected to immunoanalysis and resultant bands were visualized using ECL.
GST-pulldown assay.
GST fusion proteins were expressed in Escherichia coli and purified using glutathioneSepharose 4B beads (Amersham Pharmacia). A 1 µg sample of purified protein was incubated with protein labelled during in vitro translation [using the T7-coupled Transcription/Translation system (Promega)] in binding buffer [20 mM HEPES (pH 7·4), 100 mM NaCl, 0·5 % NP-40 and protease inhibitors]. GlutathioneSepharose 4B beads were then added and the reaction mixture was incubated at 4 °C overnight. Beads were washed four times with binding buffer and bound proteins were separated by SDS-PAGE. Radioactivity was measured by autoradiography or by using a Fujix BAS-1500 screen (Fuji).
-Gal assay of K8 transactivation function using yeast SNF5
.
The two yeast strains FY22 (MATa his3200 ura3-52) and FY1658 (MATa his3
200 ura3-52 lys2-128
snf5
2) were gifts from F. Winston (Harvard Medical School, MA, USA) and were described previously (Lee et al., 2002
). Media was prepared according to standard methods. Yeast strain FY22 and its isogenic mutant strain SNF5
(FY1658) were transformed using the lithium acetate polyethylene glycol method.
-Galactosidase activity was determined in triplicate from pools of three independently transformed colonies.
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RESULTS |
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To investigate the transcriptional activation domain of K8, we constructed a set of plasmid vectors, the pLexA/K8 series (Fig. 1A). When EGY48 transformants harbouring p8op-lacZ plus members of the pLexA/K8 series were grown on synthetic medium (-His/-Leu/-Ura), we observed that only some grew on Leu- medium. The same results were obtained using synthetic minimum medium (-His/-Ura) with X-Gal, in which
-galactosidase expression from the p8op-lacZ plasmid under the control of LexA operators was indicated by blue-coloured colonies (data not shown).
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To determine whether similar data would be obtained in a mammalian system, we constructed chimeric protein expression vectors in which Gal4DBD was fused to K8 deletion mutants (the pM/K8 series). Hybrid proteins were assayed for their ability to transactivate the Gal4-dependent promoter (pFR-luc). We found that, as in yeast, K8(1115) had much stronger transcriptional potential than wild-type K8 (Fig. 1B). Next we subcloned the same set of deletion mutants into the pcDNA3-Gal4 vector to determine protein expression levels, since the pM vector is not suitable for such analysis in our system. Similar results as those described above were obtained when these pcDNA3-Gal4 K8 constructs were tested in reporter assays (data not shown), and immunoblotting of each construct showed that the differences in transactivating ability between K8 constructs was not due to differences in protein expression (Fig. 1C
). Although there are no published data regarding K8 transactivating properties, or K8 response elements in promoters, our data suggest K8 may have domains for both transcriptional activation and suppression within K8 itself and acts as a strong transactivator under specific conditions.
K8 interacts with hSNF5 in yeast
The experiments above identified K8 deletion mutants from both the amino- and carboxyl-terminal ends that do not have transactivating properties in yeast, namely K8(175) and K8(116237). We used K8(175) in yeast two-hybrid screening since the characteristics of the amino-terminal region of K8 are relatively unknown.
To investigate cellular proteins that interact with K8(175), we performed a yeast two-hybrid assay using a B cell cDNA library. The library was cloned into the pB42AD vector (TRP1 selection marker in yeast), which contains a transcriptional activation domain and expression of activation domain-fused proteins from this vector is controlled by the Gal1 inducible promoter. About 3x105 colonies were screened in the two-hybrid assay and 37 positive clones were identified and sequenced. Five of the 37 clones contained cDNAs that encoded a truncated amino-terminal version of the hSNF5 protein, a component of the SWISNF complex (Kalpana et al., 1994). hSNF5 is the human homologue of the S. cerevisiae SNF5 protein (ySNF5) (Laurent et al., 1990
) and the proteins share 3355 % overall sequence identity and 4171 % similarity in conserved residues (Kalpana et al., 1994
).
K8 co-immunoprecipitates with hSNF5 in 293T cells
To test whether KSHV K8 interacts with hSNF5 in mammalian cells, 293T cells were transfected with no DNA (mock), GST-fused K8 expression plasmid (pEBG/K8) alone, Flag-tagged hSNF5 expression vector (pME18S/hSNF5) plus blank vector (pEBG) or pME18S/hSNF5 plus pEBG/K8. We found that addition of glutathioneSepharose beads to lysates from cells transfected with pME18S/hSNF5 plus pEBG/K8 resulted in precipitation of GST-fused K8 with FlaghSNF5 (Fig. 2A). This was not observed when using extracts from cells transfected with pME18S/hSNF5 plus blank vector. An antibody against Flag also co-precipitated Flag-tagged hSNF5 and GST-K8. These data suggest K8 and hSNF5 are associated in mammalian cells.
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K8 binds to aa 48183 of hSNF5
To determine the K8-binding domain in hSNF5, we performed binding studies, GST-pulldown assays, using in vitro-translated K8 and hSNF5-deletion mutants fused to GST (Fig. 3A). hSNF5 has three highly conserved regions (CR), two of which are imperfect repeats (CR I and CR II). The integrase (IN) of HIV and c-Myc specifically binds to CR I (Cheng et al., 1999
; Kalpana et al., 1994
; Yung et al., 2001
). Wild-type and mutant GST-fused hSNF5 were expressed, purified and incubated with in vitro-transcribed and -translated 35S-labelled K8. We found that K8 bound to GSThSNF5 but not to GST protein alone (Fig. 3B
). K8 bound to the amino-terminal end of hSNF5 (aa 1183), particularly to the regions of aa 48100 and 101183 but did not bind to the carboxyl-terminal end (aa 184385) of hSNF5. These data are consistent with those obtained from the yeast two-hybrid assay. This is the first report of a protein interacting with this portion of hSNF5.
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Transactivation by K8 and K8(1115) is affected by SNF5 in yeast
The multiprotein SWISNF complex functions by altering chromatin structure and is essential for transcriptional activation of several inducible genes (Peterson & Herskowitz, 1992). Genetic and structural data suggest that SWISNF disrupts the chromatin structure at promoters to allow transcription machinery increased access. SWISNF proteins mediate the interaction between gene-specific transactivators and general transcription factors to help general transcription machinery bind to chromatin (Lee et al., 1999
). Since we found that K8 and K8(1115) have transactivating property in yeast, their ability to interact with modifiers of chromatin structure was tested.
Both wild-type (FY22) and mutant yeast strains deficient in SNF5 (FY1658), the yeast homologue of hSNF5, were used in these studies. K8 and its carboxyl-terminal deletion mutant K8(1115) were fused to the DBD of LexA and examined for activation of a lacZ gene in wild-type and mutant yeast, as described previously (Kowenz-Leutz & Leutz, 1999). The data presented in Table 1
and Fig. 5
(A) show that LexA/K8(1115) activation of the lacZ gene was greater than that by LexA/K8 and reached a level similar to activation by LexA/Gal4DBD. In addition, these data show that lacZ gene activation by LexA/K8 and LexA/K8(1115) was affected by the presence of SNF5: SNF5 enhances the transcriptional activity of LexA/K8(1115). In accordance with published results (Laurent & Carlson, 1992
), LexA alone (negative control) did not affect expression in wild-type or mutant yeast but expression driven by the LexA/Gal4 control was SNF5 dependent (Fig. 5A
). Immunoblotting for LexA and
-actin expression in wild-type and mutant yeast strains confirmed that the differences in lacZ gene activation between constructs were not due to variations in protein levels (Fig. 5B
). These data indicate that K8- and K8(1115)-dependent gene activation in yeast requires SNF5 and probably a functional SWISNF complex.
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DISCUSSION |
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The hSNF5 (INI1 or BAF47) gene encodes a member of the SWISNF chromatin ATP-dependent remodelling complex family and is a homologue of S. cerevisiae SNF5, a transcriptional activator that acts in a complex with several other proteins, including SWI2SNF2, SNF6, SWI1 and SWI3 (the SWISNF complex) to activate genes (Kalpana et al., 1994; Laurent & Carlson, 1992
; Laurent et al., 1990
). hSNF5 appears to be present in all mammalian SWISNF complexes (Vignali et al., 2000
) and appears to be involved in HIV integration, association with PML and the HIV preintegration complex, interaction with the carboxyl-terminal SET domains of ALL-1 and c-Myc and EBV nuclear protein 2 transactivation (Cheng et al., 1999
; Kalpana et al., 1994
; Morozov et al., 1998
; Rozenblatt-Rosen et al., 1998
; Turelli et al., 2001
; Wu et al., 1996
, 2000
; Yung et al., 2001
).
Recently, hSNF5 was shown to be tumour suppressor gene located on chromosome 22q11.2 and biallelic mutations in the hSNF5/INI1 gene were shown to cause malignant rhabdoid tumours, an extremely aggressive cancer of early childhood (Versteege et al., 1998). Alterations in the hSNF5/INI1 gene are also found in chronic myeloid leukaemia, lymphoid malignancy and various malignancies of the CNS (Grand et al., 1999
; Sevenet et al., 1999a
, b
; Yuge et al., 2000
). In mice, inactivation of the SNF5/INI1 gene by homologous recombination is lethal at a very early stage and heterozygous SNF5/INI1 mutants show increased susceptibility to early onset of cancer (Klochendler-Yeivin et al., 2000
).
In this study, we used yeast two-hybrid screening to show that K8 interacts with hSNF5. In addition, K8 was found to bind to, and co-localize with, hSNF5 in mammalian cells and to co-immunoprecipitate with hSNF5 in KSHV-harbouring BCBL-1 cells. The interaction between K8 and hSNF5 required aa 48183 of hSNF5 and 175 of K8. We also found that while full-length K8 had weak transactivating properties, its carboxyl-terminal deletion mutant K8(1115) had strong activity. Of particular note was that the transactivating property of K8 and K8(1115) in yeast requires SNF5, a yeast homologue of hSNF5.
Previously, we demonstrated that KSHV K8 protein interacts with CBP and that interaction might lead to competition for limited amounts of CBP (Hwang et al., 2001). Because CBP has HAT activity and is used by viral proteins to promote viral gene transactivation (Arany et al., 1995
; Dorsman et al., 1997
; Eckner et al., 1996
; Gwack et al., 2001
), there is a possibility that K8 may function as a transcriptional activator of KSHV gene transcription, like its homologue EBV Zta. Recruitment of modifiers and remodellers to specific DNA sites within chromatin plays a critical role in controlling gene expression. Since K8 can interact functionally with chromatin remodellers, such as CBP and hSNF5, we can speculate that K8 modulates KSHV promoters and/or cellular promoters, by targeting chromatin-remodellers or -modifying factors.
Wu et al. (2001) showed the association and co-localization of K8 with the KSHV pseudoreplication compartment structure and PML in PODs. hSNF5 was also recently found to be required for efficient replication of human papillomavirus DNA and also for mammalian DNA replication, for which it acted either alone or complexed with SWISNF (Lee et al., 1999
). The data associating PML with virus replication (Adamson & Kenney, 2001
; Bell et al., 2000
) suggest further that K8 plays a role in KSHV replication. This hypothesis is also supported by reports suggesting that phosphorylation of K8 by CDKs may link KSHV DNA replication to the cell cycle (Polson et al., 2001
). Further support can be inferred from data showing p53 is sequestered in virus replication centres and that K8 recruits p53 to PODs (Fortunato & Spector, 1998
; Katano et al., 2001
).
The present work is the first to indicate that K8 may function as a transcriptional activator in the life cycle of KSHV and that there may be K8-responsive promoters. These findings are consistent with those showing K8 binds to a 300 bp sequence derived from the KSHV genome (Lin & Yuan, 2001).
Based on the present data, it may be that a complex transactivation domain is located toward the K8 amino terminus and the central region of the protein contains negative regulatory domains that can modify the transactivating function of the protein (Kowenz-Leutz et al., 1994; Williams et al., 1995
). Such an arrangement would explain the high activity of K8(1115) due to the lack of a negative regulatory domain (probably, aa 116158 of K8). The observation that K8 is phosphorylated by CDKs (Polson et al., 2001
) suggests cell cycle-dependent changes in the phosphorylation state of K8 may modulate its function, for example, by triggering differential activation of host or viral genes at different stages. Although these possibilities need more investigation, we propose that K8 functions as a transcriptional activator under specific conditions and that it acts in concert with the cellular chromatin-remodelling factor hSNF5.
K8 binding to hSNF5 may have a number of significant cellular consequences. For example, KSHV-induced tumourigenesis may be enhanced if K8 binding interferes with hSNF5 tumour suppressor activity. In addition, K8 binding to hSNF5 may influence HIV infection, since hSNF5 is also known as HIV INI1 and is important for HIV-1 virion production (Kalpana et al., 1994; Yung et al., 2001
). Also, K8 may function as a link between KSHV and HIV, since Kaposi's sarcoma is the most common tumour associated with HIV-1 infection (Blattner, 1999
; Reitz et al., 1999
). Ongoing study will focus on the contribution of hSNF5 to these events.
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ACKNOWLEDGEMENTS |
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REFERENCES |
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---|
Arany, Z., Newsome, D., Oldread, E., Livingston, D. M. & Eckner, R. (1995). A family of transcriptional adaptor proteins targeted by the E1A oncoprotein. Nature 374, 8184.[CrossRef][Medline]
Bell, P., Lieberman, P. M. & Maul, G. G. (2000). Lytic but not latent replication of EpsteinBarr virus is associated with PML and induces sequential release of nuclear domain 10 proteins. J Virol 74, 1180011810.
Blattner, W. A. (1999). Human retroviruses: their role in cancer. Proc Assoc Am Physicians 111, 563572.[Medline]
Boshoff, C. & Weiss, R. A. (1998). Kaposi's sarcoma-associated herpesvirus. Adv Cancer Res 75, 5786.[Medline]
Boshoff, C., Schulz, T. F., Kennedy, M. M., Graham, A. K., Fisher, C., Thomas, A., McGee, J. O., Weiss, R. A. & O'Leary, J. J. (1995). Kaposi's sarcoma-associated herpesvirus infects endothelial and spindle cells. Nat Med 1, 12741278.[Medline]
Cesarman, E., Chang, Y., Moore, P. S., Said, J. W. & Knowles, D. M. (1995). Kaposi's sarcoma-associated herpesvirus-like DNA sequences in AIDS-related body-cavity-based lymphomas. N Engl J Med 332, 11861191.
Cheng, S.-W. G., Davies, K. P., Yung, E., Beltran, R. J., Yu, J. & Kalpana, G. V. (1999). c-Myc interacts with INI1/hSNF5 and requires the SWI/SNF complex for transactivation function. Nat Genet 22, 102105.[CrossRef][Medline]
Dorsman, J. C., Teunisse, A. F., Zantema, A. & van der Eb, A. J. (1997). The adenovirus 12 E1A proteins can bind directly to proteins of the p300 transcription co-activator family, including the CREB-binding protein CBP and p300. J Gen Virol 78, 423426.[Abstract]
Eckner, R., Ludlow, J. W., Lill, N. L., Oldread, E., Arany, Z., Modjtahedi, N., DeCaprio, J. A., Livingston, D. M. & Morgan, J. A. (1996). Association of p300 and CBP with simian virus 40 large T antigen. Mol Cell Biol 16, 34543464.[Abstract]
Fortunato, E. A. & Spector, D. H. (1998). p53 and RPA are sequestered in viral replication centers in the nuclei of cells infected with human cytomegalovirus. J Virol 72, 20332039.
Graham, F. L. & van der Eb, A. J. (1973). A new technique for the assay of infectivity of human adenovirus 5 DNA. Virology 52, 456467.[Medline]
Grand, F., Kulkarni, S., Chase, A., Goldman, J. M., Gordon, M. & Cross, N. C. P. (1999). Frequent deletion of hSNF5/INI1, a component of the SWI/SNF complex, in chronic myeloid leukemia. Cancer Res 59, 38703874.
Gruffat, H., Portes-Sentis, S., Sergeant, A. & Manet, E. (1999). Kaposi's sarcoma-associated herpesvirus (human herpesvirus-8) encodes a homologue of the EpsteinBarr virus bZip protein EB1. J Gen Virol 80, 557561.[Abstract]
Guarante, L. (1983). Promoters and lacZ fusions designed to study expression of cloned genes in yeast. Methods Enzymol 101, 181193.[Medline]
Gwack, Y., Byun, H., Hwang, S., Lim, C. & Choe, J. (2001). CREB-binding protein and histone deacetylase regulate the transcriptional activity of Kaposi's sarcoma-associated herpesvirus open reading frame 50. J Virol 75, 19091917.
Hwang, S., Gwack, Y., Byun, H., Lim, C. & Choe, J. (2001). The Kaposi's sarcoma-associated herpesvirus K8 protein interacts with CREB-binding protein (CBP) and represses CBP-mediated transcription. J Virol 75, 95099516.
Kalpana, G. V., Marmon, S., Wang, S., Crabtree, G. R. & Goff, S. P. (1994). Binding and stimulation of HIV-1 integrase by a human homolog of yeast transcription factor SNF5. Science 266, 20022006.[Medline]
Katano, H., Ogawa-Goto, K., Hasegawa, H., Kurata, T. & Sata, T. (2001). Human-herpesvirus-8-encoded K8 protein colocalizes with the promyelocytic leukemia protein (PML) bodies and recruits p53 to the PML bodies. Virology 286, 446455.[CrossRef][Medline]
Klochendler-Yeivin, A., Fiette, L., Barra, J., Muchardt, C., Babinet, C. & Yaniv, M. (2000). The murine SNF5/INI1 chromatin remodeling factor is essential for embryonic development and tumor suppression. EMBO Rep 1, 500506.
Kornberg, R. D. & Lorch, Y. (1999). Twenty-five years of the nucleosome, fundamental particle of the eukaryote chromosome. Cell 98, 285294.[Medline]
Kowenz-Leutz, E. & Leutz, A. (1999). A C/EBP isoform recruits the SWI/SNF complex to activate myeloid genes. Mol Cell 4, 735743.[Medline]
Kowenz-Leutz, E., Twamley, G., Ansieau, S. & Leutz, A. (1994). Novel mechanism of C/EBP (NF-M) transcriptional control: activation through derepression. Genes Dev 8, 27812791.[Abstract]
Laurent, B. C. & Carlson, M. (1992). Yeast SNF2/SWI2, SNF5, and SNF6 proteins function coordinately with the gene-specific transcriptional activators GAL4 and Bicoid. Genes Dev 6, 17071715.[Abstract]
Laurent, B. C., Treitel, M. A. & Carlson, M. (1990). The SNF5 protein of Saccharomyces cerevisiae is a glutamine- and proline-rich transcriptional activator that affects expression of a broad spectrum of genes. Mol Cell Biol 10, 56165625.[Medline]
Lee, D., Sohn, H., Kalpana, G. V. & Choe, J. (1999). Interaction of E1 and hSNF5 proteins stimulate replication of human papillomavirus DNA. Nature 399, 487491.[CrossRef][Medline]
Lee, D., Kim, J. W., Seo, T., Hwang, S. G., Choi, E. J. & Choe, J. (2002). SWI/SNF complex interacts with tumor suppressor p53 and is necessary for the activation of p53-mediated transcription. J Biol Chem 277, 2233022337.
Lin, C. L. & Yuan, Y. (2001). Expression pattern and DNA-binding property of KSHV ORF K8. 4th International Workshop on KSHV and Related Agents (California, USA, 58 August, 2001).
Lin, S. F., Robinson, D. R., Miller, G. & Kung, H. J. (1999). Kaposi's sarcoma-associated herpesvirus encodes a bZIP protein with homology to BZLF1 of EpsteinBarr virus. J Virol 73, 19091917.
Lukac, D. M., Renne, R., Kirshner, J. R. & Ganem, D. (1998). Reactivation of Kaposi's sarcoma-associated herpesvirus infection from latency by expression of the ORF 50 transactivator, a homolog of the EBV R protein. Virology 252, 304312.[CrossRef][Medline]
Miller, G., Heston, L., Grogan, E. & 7 other authors (1997). Selective switch between latency and lytic replication of Kaposi's sarcoma herpesvirus and EpsteinBarr virus in dually infected body cavity lymphoma cells. J Virol 71, 314324.[Abstract]
Morozov, A., Yung, E. & Kalpana, G. V. (1998). Structure-function analysis of integrase interactor 1/hSNF5L1 reveals differential properties of two repeat motifs present in the highly conserved region. Proc Natl Acad Sci U S A 95, 11201125.
Muchardt, C. & Yaniv, M. (1999). The mammalian SWI/SNF complex and the control of cell growth. Semin Cell Dev Biol 10, 189195.[CrossRef][Medline]
Muchardt, C. & Yaniv, M. (2001). When the SWI/SNF complex remodels the cell cycle. Oncogene 20, 30673075.[CrossRef][Medline]
Park, J., Seo, T., Hwang, S., Lee, D., Gwack, Y. & Choe, J. (2000). The K-bZIP protein from Kaposi's sarcoma-associated herpesvirus interacts with p53 and represses its transcriptional activity. J Virol 74, 1197711982.
Peterson, C. L. & Herskowitz, I. (1992). Characterization of the yeast SWI1, SWI2, and SWI3 genes, which encode a global activator of transcription. Cell 68, 573583.[Medline]
Polson, A. G., Huang, L., Lukac, D. M., Blethrow, J. D., Morgan, D. O., Burlingame, A. L. & Ganem, D. (2001). Kaposi's sarcoma-associated herpesvirus K-bZIP protein is phosphorylated by cyclin-dependent kinases. J Virol 75, 31753184.
Portes-Sentis, S., Manet, E., Gourru, G., Sergeant, A. & Gruffat, H. (2001). Identification of a short amino acid sequence essential for efficient nuclear targeting of the Kaposi's sarcoma-associated herpesvirus/human herpesvirus-8 K8 protein. J Gen Virol 82, 507512.
Reitz, M. S., Jr, Nerurkar, L. S. & Gallo, R. C. (1999). Perspective on Kaposi's sarcoma: facts, concepts, and conjectures. J Natl Cancer Inst 91, 14531458.
Renne, R., Zhong, W., Herndier, B., McGrath, M., Abbey, N., Kedes, D. & Ganem, D. (1996). Lytic growth of Kaposi's sarcoma-associated herpesvirus (human herpesvirus 8) in culture. Nat Med 2, 342346.[Medline]
Rozenblatt-Rosen, O., Rozovskaia, T., Burakov, D. & 7 other authors (1998). The C-terminal SET domains of ALL-1 and TRITHORAX interact with the INI1 and SNR1 proteins, components of the SWI/SNF complex. Proc Natl Acad Sci U S A 95, 41524157.
Russo, J. J., Bohenzky, R. A., Chien, M. C. & 8 other authors (1996). Nucleotide sequence of the Kaposi sarcoma-associated herpesvirus (HHV8). Proc Natl Acad Sci U S A 93, 1486214867.
Schulz, T. F. (1998). Kaposi's sarcoma-associated herpesvirus (human herpesvirus-8). J Gen Virol 79, 15731591.
Sevenet, N., Lellouch-Tubiana, A., Schofield, D., Hoang-Xuan, K., Gessler, M., Birnbaum, D., Jeanpierre, C., Jouvet, A. & Delattre, O. (1999a). Spectrum of hSNF5/INI1 somatic mutations in human cancer and genotype-phenotype correlations. Hum Mol Genet 8, 23592368.
Sevenet, N., Sheridan, E., Amram, D., Schneider, P., Handgretinger, R. & Delattre, O. (1999b). Constitutional mutations of the hSNF5/INI1 gene predispose to a variety of cancers. Am J Hum Genet 65, 13421348.[CrossRef][Medline]
Shiio, Y., Yamamoto, T. & Yamaguchi, N. (1992). Negative regulation of Rb expression by the p53 gene product. Proc Natl Acad Sci U S A 89, 52065210.[Abstract]
Soulier, J., Grollet, L., Oksenhendler, E., Cacoub, P., Cazals-Hatem, D., Babinet, P., d'Agay, M. F., Clauvel, J. P., Raphael, M. & Degos, L. (1995). Kaposi's sarcoma-associated herpesvirus-like DNA sequences in multicentric Castleman's disease. Blood 86, 276280.
Sun, R., Lin, S. F., Gradoville, L., Yuan, Y., Zhu, F. & Miller, G. (1998). A viral gene that activates lytic cycle expression of Kaposi's sarcoma-associated herpesvirus. Proc Natl Acad Sci U S A 95, 1086610871.
Sun, R., Lin, S. F., Staskus, K., Gradoville, L., Grogan, E., Haase, A. & Miller, G. (1999). Kinetics of Kaposi's sarcoma-associated herpesvirus gene expression. J Virol 73, 22322242.
Turelli, P., Doucas, V., Craig, E., Mangeat, B., Klages, N., Evans, R., Kalpana, G. V. & Trono, D. (2001). Cytoplasmic recruitment of INI1 and PML on incoming HIV preintegration complexes: interference with early steps of viral replication. Mol Cell 7, 12451254.[CrossRef][Medline]
Versteege, I., Sevenet, N., Lange, J., Rousseau-Merck, M., Ambros, P., Handgretinger, R., Aurias, A. & Delattre, O. (1998). Truncating mutations of hSNF5/INI1 in aggressive paediatric cancer. Nature 394, 203206.[CrossRef][Medline]
Vignali, M., Hassan, A. H., Neely, K. E. & Workman, J. L. (2000). ATP-dependent chromatin-remodeling complexes. Mol Cell Biol 20, 18991910.
Williams, S. C., Baer, M., Dillner, A. J. & Johnson, P. F. (1995). CRP2 (C/EBP) contains a bipartite regulatory domain that controls transcriptional activation, DNA binding and cell specificity. EMBO J 14, 31703183.[Abstract]
Wu, D. Y., Kalpana, G. V., Goff, S. P. & Schubach, W. H. (1996). EpsteinBarr virus nuclear protein 2 (EBNA2) binds to a component of the human SNFSWI complex, hSNF5/INI1. J Virol 70, 60206028.[Abstract]
Wu, D. Y., Krumm, A. & Schubach, W. H. (2000). Promoter-specific targeting of human SWISNF complex by EpsteinBarr virus nuclear protein 2. J Virol 74, 88938903.
Wu, F. Y., Ahn, J. H., Alcendor, D. J., Jang, W. J., Xiao, J., Hayward, S. D. & Hayward, G. S. (2001). Origin-independent assembly of Kaposi's sarcoma-associated herpesvirus DNA replication compartments in transient cotransfection assays and association with the ORF-K8 protein and cellular PML. J Virol 75, 14871506.
Yuge, M., Nagai, H., Uchida, T., Murate, T., Hayashi, Y., Hotta, T., Saito, H. & Kinoshita, T. (2000). hSNF5/INI1 gene mutations in lymphoid malignancy. Cancer Genet Cytogenet 122, 3742.[CrossRef][Medline]
Yung, E., Sorin, M., Pal, A., Craig, E., Morozov, A., Delattre, O., Kappes, J., Ott, D. & Kalpana, G. V. (2001). Inhibition of HIV-1 virion production by a transdominant mutant of integrase interactor 1. Nat Med 7, 920926.[CrossRef][Medline]
Zhu, F. X., Cusano, T. & Yuan, Y. (1999). Identification of the immediate-early transcripts of Kaposi's sarcoma-associated herpesvirus. J Virol 73, 55565567.
Received 9 July 2002;
accepted 13 November 2002.