Fli-1b is generated by usage of differential splicing and alternative promoter

Dhulipala, Prasad; Leo, Lee; Rao, V. N.; Reddy, E. S. P.

doi:10.1038/sj.onc.1202030

Cited by 21 publications

(11 citation statements)

References 38 publications

(57 reference statements)

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“…These DNA-binding mutants showed significant antiapoptotic activity (compared to that of wild type) ( Figure 1c). Fli-1b, which has a slightly different amino-terminal region due to alternative splicing, showed an activity similar to Fli-1 (Dhulipala et al, 1998). These results were further confirmed by MTT viability analysis and TUNNEL assays, followed by FACS analysis (data not shown).…”

Section: Ews-fli-1 and Fli-1 Mutants That Are Deficient In Transcriptsupporting

confidence: 68%

Role of protein–protein interactions in the antiapoptotic function of EWS-Fli-1

et al. 2004

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In the majority of Ewing's family tumors, chromosomal translocation t(11;22) leads to aberrant fusion of RNAbinding protein EWS with DNA-binding ETS transcriptional factor Fli-1. EWS-Fli-1 has altered the transcriptional activity and modulating its downstream target genes through this transcriptional activity is thought to be responsible for this tumor. We have previously shown that both EWS-Fli-1 and Fli-1 have antiapoptotic activity against several apoptotic inducers. Here, we show that the transcriptional activity of EWS-Fli-1 and Fli-1 is not essential for its antiapoptotic activity. We also demonstrate that EWS-Fli-1 and Fli-1 interact with CBP through its amino-terminal region and inhibit the CBPdependent transcriptional activity of RXR. This activity appears to be independent of DNA-binding activity of EWS-Fli-1. Introduction of the dominant-negative form of CBP into Ewing's sarcoma cells sensitizes these cells against genotoxic or retinoic-acid induced apoptosis. These results suggest that the ability of EWS-Fli-1/Fli-1 to target transcriptional cofactor(s) and modulate apoptotic pathways may be responsible for its antiapoptotic and tumorigenic activities.

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Section: Ews-fli-1 and Fli-1 Mutants That Are Deficient In Transcriptsupporting

confidence: 68%

Role of protein–protein interactions in the antiapoptotic function of EWS-Fli-1

et al. 2004

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“…This region includes the distal and proximal promoters (Barat et al, 2000;Barbeau et al, 1996;Dhulipala et al, 1998). To define the sequences necessary to drive expression in lymphocytes, successive deletions from the 5' end of the amplified Fli1 sequence were made, generating a series of Fli1 promoter/reporter (P/R) constructs (Fig.…”

Section: Three Ets Binding Sites Contribute To Positive and Negative mentioning

confidence: 99%

Ets factors and a newly identified polymorphism regulate Fli1 promoter activity in lymphocytes

Nowling¹,

Fulton²,

Chike-Harris³

et al. 2008

Molecular Immunology

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Fli1 is an Ets family member that is essential for embryonic development. Increasing evidence suggests modulating Fli1 gene expression impacts lymphocyte development/function and is an important mediator in the autoimmune disease lupus. Fli1 is over-expressed in splenic lymphocytes in lupus prone mouse strains and in PBMCs of lupus patients. Presently, it is unknown how Fli1 gene expression is controlled in lymphocytes or how it becomes over-expressed in lupus. Therefore, we examined Fli1 regulation in a murine B cell line and T cell line and identified several cis-regulatory elements within a 230 bp region that contribute to Fli1 promoter activity. Ets factors Elf1, Tel and Fli1 bind in vitro to this region and increase endogenous Fli1 expression when over-expressed in a T cell line. In addition, we determined that a microsatellite located adjacent to the region containing these cis-regulatory elements is polymorphic in three lupus prone mouse strains and that the length of the microsatellite is inversely correlated with promoter activity in a T cell line. These results suggest that several Ets factors, including Fli1 itself, are involved in the transcriptional regulation of Fli1 in lymphocytes. Furthermore, the presence of a polymorphic microsatellite in the Fli1 promoter may contribute to increased Fli1 expression in T cells during lupus disease progression.

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“…35 Similarly, Ets family member Fli-1 was also stably expressed. Expression of Fli-1 has been reported in human T-cell, B-cell, and myeloid leukemia cell lines 36 and was shown to be critical for hematopoiesis in a Fli-1-deficient mouse. 37 Expression of the aldoketo reductase mAKRa, whose function has not yet been elucidated, was restricted to the ECoM-G clone and was stable throughout differentiation in contrast to a previous report that showed decreased expression following the alltrans-RA (atRA)-induced granulocytic differentiation of EML-C1 and MPRO cells.…”

Section: Ecom-g and Ecom-m Cells Exhibit Lineage-specific And Differementioning

confidence: 99%

Estrogen-dependent E2a/Pbx1 myeloid cell lines exhibit conditional differentiation that can be arrested by other leukemic oncoproteins

Sykes

Kamps

2001

Blood

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The molecular pathways of normal myeloid differentiation, as well as the mechanisms by which oncogenes disrupt this process, remain poorly understood. A major limitation in approaching this problem has been the lack of suitable cell lines that exhibit normal, terminal, and synchronous differentiation in the absence of endogenous oncoproteins and in response to physiologic cytokines, and whose differentiation can be arrested by ectopically expressed human oncoproteins. This report describes clonal, granulocyte-macrophage colony-stimulating factor-dependent myeloid cell lines that exhibit these properties. The cell lines were established by conditional immortalization of primary murine marrow progenitors with an estrogen-regulated E2a/Pbx1-estrogen receptor fusion protein. Clones were identified that proliferated as immortalized blasts in the presence of estrogen, and that exhibited granulocytic, monocytic, or bipotential (granulocytic and monocytic) differentiation on estrogen withdrawal. Differentiation was normal and terminal as evidenced by morphology, cell surface markers, gene expression, and functional assays. The differentiation of the cells could be arrested by heterologous oncoproteins including AML1/ETO, PML/RAR␣, PLZF/RAR␣, Nup98/HoxA9, and other Hox proteins. Furthermore, the study examined the effects of cooperating oncoproteins such as Ras or Bcr/Abl, which allowed for both factor-independent proliferation and differentiation, or Bcl-2, which permitted factor-independent survival but not proliferation. These myeloid cell lines provide tools for examining the biochemical and genetic pathways that accompany normal differentiation as well as a system in which to dissect how other leukemic oncoproteins interfere with these pathways. (Blood. 2001; 98:2308-2318)

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Fli-1b is generated by usage of differential splicing and alternative promoter

Cited by 21 publications

References 38 publications

Role of protein–protein interactions in the antiapoptotic function of EWS-Fli-1

Role of protein–protein interactions in the antiapoptotic function of EWS-Fli-1

Ets factors and a newly identified polymorphism regulate Fli1 promoter activity in lymphocytes

Estrogen-dependent E2a/Pbx1 myeloid cell lines exhibit conditional differentiation that can be arrested by other leukemic oncoproteins

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