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Dive into the research topics where Ann Jansson is active.

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Featured researches published by Ann Jansson.


Journal of General Virology | 1995

PU box-binding transcription factors and a POU domain protein cooperate in the Epstein-Barr virus (EBV) nuclear antigen 2-induced transactivation of the EBV latent membrane protein 1 promoter.

Anna Sjöblom; Ann Jansson; Weiwen Yang; Sonia Laín; Tina Nilsson; Lars Rymo

Expression of the Epstein-Barr virus (EBV) latent membrane protein (LMP1) is regulated by virus- and host cell-specific factors. The EBV nuclear antigen 2 (EBNA2) has been shown to transactivate a number of viral and cellular gene promoters including the promoter for the LMP1 gene. EBNA2 is targeted to at least some of these promoters by interacting with a cellular DNA binding protein, RBP-J kappa. In the present report we confirm and extend our previous observation that the LMP1 promoter can be activated by EBNA2 in the absence of the RBP-J kappa-binding sequence in the LMP1 promoter regulatory region (LRS). We show that two distinct LRS regions, -106 to +40 and -176 to -136, contribute to EBNA2 responsiveness. Site-directed mutagenesis analysis of the upstream -176/-136 EBNA2 responsive element revealed that two critical cis-acting elements are required for full promoter function. These same elements analysed by electrophoretic mobility shift assays define two binding sites recognized by nuclear factors derived from B cells. An octamer-like sequence (-147 to -139) contained overlapping binding sites for an unidentified transcriptional repressor on the one hand and a factor(s) belonging to the POU domain family but distinct from Oct-1 and Oct-2 on the other. An adjacent purine tract (-171 to -155) held a PU.1 binding site, which was also recognized by a related factor. The results suggest that the POU domain protein and either of two PU box-binding factors bind simultaneously to LRS, creating a ternary complex that might be in part responsible for mediating the transactivation of the LMP1 promoter by EBNA2. There were no qualitative differences between EBV-negative and EBV-positive cells with regard to transcription factor binding to the octamer-like sequence and the PU.1 recognition site, as revealed by electrophoretic mobility shift assays.


Journal of General Virology | 1995

Domains of the Epstein-Barr virus nuclear antigen 2 (EBNA2) involved in the transactivation of the latent membrane protein 1 and the EBNA Cp promoters

Anna Sjöblom; Annika Nerstedt; Ann Jansson; Lars Rymo

The Epstein-Barr virus (EBV) nuclear antigen 2 (EBNA2) is one of the first EBV-encoded gene products expressed after infection of primary B lymphocytes. EBNA2 is essential for the growth-transforming potential of the virus and it functions as a transcriptional activator of a set of viral and cellular genes. Sequence-specific DNA-binding by EBNA2 has not been demonstrated but the molecule is targeted to specific DNA regions by a cellular protein, RBP-J kappa, which recognizes the GTGGGAA sequence present in the regulatory region of all EBNA2-responsive promoters defined so far. We have determined the contribution of a RBP-J kappa recognition sequence, an adjacent interferon-stimulated response element (ISRE) motif and a PU.1-binding site in the LMP1 regulatory sequence (LRS) to EBNA2-induced transactivation of the promoter by site-directed mutagenesis of LRS-carrying reporter plasmids. EBNA2 responsiveness was reduced by approximately twofold when either or both of the RBP-J kappa-binding and ISRE sequences were mutated. ISRE seemed to function as an EBNA2-independent positive element. On the other hand, mutation of the PU box resulted in a drastic reduction of EBNA2 responsiveness, irrespective of whether the RBP-J kappa site or the ISRE motif was present. A comparative study by deletion mutation identified regions of EBV B95-8 EBNA2 involved in the transactivation of the LMP1 and the EBNA Cp promoters. Two domains of EBNA2 defined by deletion of amino acids 247-337 and 437-476 were found to be important for the activation of both promoters, while two different domains corresponding to residues 4-18 and 118-198 were required solely for the LMP1 promoter. Thus, EBNA2 must activate the LMP1 and Cp promoters by different mechanisms. All deletions involved in transcriptional activation of the two promoters contained regions that are conserved in EBNA2 of B95-8 EBV (type 1), AG876 EBV (type 2) and herpesvirus papio origin.


Journal of Virology | 2009

Nuclear Factor-κB Binds to the Epstein-Barr Virus LMP1 Promoter and Upregulates Its Expression

Pegah Johansson; Ann Jansson; Ulla Rüetschi; Lars Rymo

ABSTRACT The latent membrane protein 1 (LMP1) oncogene carried by Epstein-Barr virus (EBV) is essential for transformation and maintenance of EBV-immortalized B cells in vitro, and it is expressed in most EBV-associated tumor types. The activation of the NF-κB pathway by LMP1 plays a critical role in the upregulation of antiapoptotic proteins. The EBV-encoded EBNA2 transactivator is required for LMP1 activation in latency III, while LMP1 itself appears to be critical for its activation in the latency II gene expression program. In both cases, additional viral and cellular transcription factors are required in mediating transcription activation of the LMP1 promoter. Using DNA affinity purification and chromatin immunoprecipitation assay, we showed here that members of the NF-κB transcription factor family bound to the LMP1 promoter in vitro and in vivo. Electrophoretic mobility shift assay analyses indicated the binding of the p50-p50 homodimer and the p65-p50 heterodimer to an NF-κB site in the LMP1 promoter. Transient transfections and reporter assays showed that the LMP1 promoter is activated by exogenous expression of NF-κB factors in both B cells and epithelial cells. Exogenous expression of NF-κB factors in the EBNA2-deficient P3HR1 cell line induced LMP1 protein expression. Overall, our data are consistent with the presence of a positive regulatory circuit between NF-κB activation and LMP1 expression.


Genes and Immunity | 2009

The Sp1 transcription factor binds to the G-allele of the –1087 IL-10 gene polymorphism and enhances transcriptional activation

Lena Larsson; Pegah Johansson; Ann Jansson; Mauro Donati; Lars Rymo; Tord Berglundh

The objectives of this study were to evaluate the influence of the −1087 single nucleotide polymorphism (SNP) on the gene expression of interleukin (IL)-10 and to identify transcription factors binding to this site in B cells. Using electrophoretic mobility-shift assays and nuclear extract from the DG75 B-cell line, we demonstrated that the Sp1 transcription factor bound to the −1087 G-allele of the IL-10 promoter and that the transcription factors PU.1 and Spi-B bound to both the G- and A-alleles. Transient transfections showed that lipopolysaccharide stimulation resulted in a 15-fold increase in promoter activity for the G-allele as compared to a 6-fold increase for the A-allele. Co-transfection with Sp1 expression vector in Sp1-deficient SL2 cells leading to Sp1 binding to the G-allele of the −1087 SNP resulted in increased IL-10 promoter activity. The results suggest a role for Sp1 transcription factor in the activation of IL-10 through the G-allele of the −1087 SNP in response to inflammatory signals.


Virus Genes | 2007

Role of a consensus AP-2 regulatory sequence within the Epstein-Barr Virus LMP1 promoter in EBNA2 mediated transactivation

Ann Jansson; Pegah Johansson; Weiwen Yang; Lars Palmqvist; Anna Sjöblom-Hallén; Lars Rymo

The Epstein-Barr virus (EBV) tumor-associated latent membrane protein 1 (LMP1) gene expression is transactivated by EBV nuclear antigen 2 (EBNA2) in human B cells. We previously reported that an E-box element at the LMP1 regulatory sequence (LRS) represses transcription of the LMP1 gene through the recruitment of a Max-Mad1-mSin3A complex. In the present study, using deletion/mutation analysis, and electrophoretic mobility shift assays, we show that the promoter region adjacent to the E-box (−59/−67) is required for the full repression conferred by E-box binding proteins. The repressive effect of these factors was overcome by an inhibitor of histone deacetylation, Trichostatin A (TSA), concurring with the reports that histone deacetylation plays an important role in repression mediated by Max-Mad1-mSin3A complex. Furthermore, ChIP analyses showed that histones at the transcriptionally active LMP1 promoter were hyperacetylated, whereas in the absence of transcription they were hypoacetylated. EBNA2 activation of the promoter required a consensus AP-2 sequence in the −103/−95 LRS region. While EMSA results and the low level of AP-2 factors expression in B cells argue against known AP-2 factors binding to this site, several pieces of evidence point to a similar mechanism of promoter activation as seen by AP-2 factors. We conclude that an AP-2 site-binding factor and EBNA2 act in concert to overcome the repression of the LMP1 promoter via the consensus AP-2 site. This activation showed strong correlation with histone hyperacetylation at the promoter, indicating this to be a major mechanism for the EBNA2 mediated LMP1 transactivation.


Journal of Virology | 2010

The p38 Signaling Pathway Upregulates Expression of the Epstein-Barr Virus LMP1 Oncogene

Pegah Johansson; Ann Jansson; Ulla Rüetschi; Lars Rymo

ABSTRACT The Epstein-Barr virus (EBV)-encoded LMP1 oncogene has a role in transformation, proliferation, and metastasis of several EBV-associated tumors. Furthermore, LMP1 is critically involved in transformation and growth of EBV-immortalized B cells in vitro. The oncogenic properties of LMP1 are attributed to its ability to upregulate anti-apoptotic proteins and growth signals. The transcriptional regulation of LMP1 is dependent on the context of cellular and viral proteins present in the cell. Here, we investigated the effect of several signaling pathways on the regulation of LMP1 expression. Inhibition of p38 signaling, using p38-specific inhibitors SB203580 and SB202190, downregulated LMP1 in estrogen-induced EREB2.5 cells. Similarly, p38 inhibition decreased trichostatin A-induced LMP1 expression in P3HR1 cells. Exogenous expression of p38 in lymphoblastoid cell lines (LCLs) led to an increase in LMP1 promoter activity in reporter assays, and this activation was mediated by the previously identified CRE site in the promoter. Inhibition of p38 by SB203580 and p38-specific small interfering RNA (siRNA) also led to a modest decrease in endogenous LMP1 expression in LCLs. Chromatin immunoprecipitation indicated decreased binding of CREB-ATF1 to the CRE site in the LMP1 promoter after inhibition of the p38 pathway in EREB2.5 cells. Taken together, our results suggest that an increase in p38 activation upregulates LMP1 expression. Since p38 is activated in response to stimuli such as stress or possibly primary infection, a transient upregulation of LMP1 in response to p38 may allow the cells to escape apoptosis. Since the p38 pathway itself is activated by LMP1, our results also suggest the presence of an autoregulatory loop in LMP1 upregulation.


Journal of General Virology | 2002

The Epstein–Barr virus ZEBRA protein activates transcription from the early lytic F promoter by binding to a promoter-proximal AP-1-like site

Henrik Zetterberg; Ann Jansson; Lars Rymo; Fu Chen; Ann Karlsson; Georg Klein; Bertha Brodin

The ZEBRA protein encoded by the Epstein-Barr virus (EBV) genome activates a switch from the latent to the lytic gene expression programme of the virus. ZEBRA, a member of the basic leucine zipper family of DNA-binding proteins, is a transcriptional activator capable of inducing expression from several virus lytic cycle promoters by binding to activator protein 1 (AP-1)-like sites. The Epstein-Barr virus BamHI F promoter, Fp, was for some time believed to initiate EBNA1-specific transcription in EBV-transformed latent cells. More recent data, however, show that Fp is an early lytic promoter and that the dominant EBNA1 gene promoter in latent cells is Qp, located about 200 bp downstream of Fp. In the present investigation we confirm that Fp displays the characteristics of a lytic promoter. Fp is downregulated in latently EBV-infected cells, both in the endogenous virus genome and in reporter plasmids that carry Fp regulatory sequences upstream of position -136 and down to +10 relative to the Fp transcription start site (+1), and is activated on induction of the virus lytic cycle. We show that the repression of Fp in latent stages of infection can be abolished by ZEBRA, and demonstrate that ZEBRA activates Fp through a direct interaction with an AP-1-like site at position -52/-46 in the promoter-proximal Fp region.


Oncogene | 2017

Upregulation of Flt3 is a passive event in Hoxa9/Meis1-induced acute myeloid leukemia in mice.

Anna Staffas; Laleh S. Arabanian; Stella Yuan Wei; Ann Jansson; Sara Ståhlman; Peter Johansson; Linda Fogelstrand; Jörg Cammenga; Florian Kuchenbauer; Lars Palmqvist

HOXA9, MEIS1 and FLT3 are genes frequently upregulated in human acute myeloid leukemia. Hoxa9 and Meis1 also cooperate to induce aggressive AML with high Flt3 expression in mice, suggesting an important role for Flt3 in Hoxa9/Meis1-induced leukemogenesis. To define the role of Flt3 in AML with high Hoxa9/Meis1, we treated mice with Hoxa9/Meis1-induced AML with the Flt3 inhibitor AC220, used an Flt3-ligand (FL−/−) knockout model, and investigated whether overexpression of Flt3 could induce leukemia together with overexpression of Hoxa9. Flt3 inhibition by AC220 did not delay AML development in mice transplanted with bone marrow cells overexpressing Hoxa9 and Meis1. In addition, Hoxa9/Meis1 cells induced AML in FL−/− mice as rapid as in wild-type mice. However, FL−/− mice had reduced organ infiltration compared with wild-type mice, suggesting some Flt3-dependent effect on leukemic invasiveness. Interestingly, leukemic Hoxa9/Meis1 cells from sick mice expressed high levels of Flt3 regardless of presence of its ligand, showing that Flt3 is a passive marker on these cells. In line with this, combined engineered overexpression of Flt3 and Hoxa9 did not accelerate the progression to AML. We conclude that the Hoxa9- and Meis1-associated upregulation of Flt3 is not a requirement for leukemic progression induced by Hoxa9 and Meis1.


Experimental hematology & oncology | 2015

Mutated NPM1 in combination with overexpression of Meis1 or Hoxa9 is not sufficient to induce acute myeloid leukemia

Hanna Grauers Wiktorin; Tina Nilsson; Ann Jansson; Lars Palmqvist; Anna Martner

BackgroundAcute myeloid leukemia (AML) carrying nucleophosmin 1 (NPM1) mutations (NPMc+) is regarded as a separate entity of myeloid neoplasms due to its distinct biological and clinical features. However, NPMc+ alone displays low leukemogenic activity and cooperating events appear crucial for AML to develop. Dysregulation of homeobox genes, such as HOXA9 and MEIS1, is a common transcriptional signature of NPMc+ AML. Furthermore, the pathogenic role for NPMc+ in AML remains incompletely understood.AimTo elucidate if NPMc+ collaborates with Meis1 or Hoxa9 in the evolvement of AML.MethodsMurine bone marrow cells were genetically engineered to express mutated NPM1 variant A in combination with overexpression of Meis1 or Hoxa9. The capacity of the transduced cells to transform in vitro and to cause leukemia in vivo was then assessed.Findings and conclusionThere was no synergy between NPMc+ and Meis1 or Hoxa9 in causing leukemogenic transformation of murine bone marrow cells, or in inducing AML in a transplantation model. Hence, overexpression of Meis1 or Hoxa9 in combination with NPMc+ expression was not sufficient to generate an NPMc+ AML mouse model.


Journal of Virology | 1998

An ATF/CRE Element Mediates both EBNA2-Dependent and EBNA2-Independent Activation of the Epstein-Barr Virus LMP1 Gene Promoter

Anna Sjöblom; Weiwen Yang; Lars Palmqvist; Ann Jansson; Lars Rymo

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Lars Rymo

Sahlgrenska University Hospital

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Lars Palmqvist

Sahlgrenska University Hospital

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Anna Sjöblom

Sahlgrenska University Hospital

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Pegah Johansson

Sahlgrenska University Hospital

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Weiwen Yang

University of Gothenburg

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Tina Nilsson

Sahlgrenska University Hospital

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Anna Staffas

University of Gothenburg

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