ETS transcription factors and regulation of immunity

Gallant, Sarah; Gilkeson, Gary S.

doi:10.1007/s00005-006-0017-z

Cited by 153 publications

(133 citation statements)

References 195 publications

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“…These findings fit well with the current understanding of the role of the transcription factors of the ETS family in controlling the expression of a wide variety of genes in hemopoietic and other cell types (13)(14)(15). Ets factors share a common DNA binding motif, the ets domain, which has been shown to be a variation of the winged helix-turn-helix motif (35).…”

Section: Discussionsupporting

confidence: 85%

“…Ets-2 is a member of the ETS family of transcription factors that bind to purine-rich DNA sequences with GGA(A/T) as a central core consensus through a highly conserved DNA binding domain (13,14). Ets proteins function as activators or repressors of transcription in partnership with other DNA-binding proteins and coregulators and control the expression of genes involved in diverse biological functions, such as mitosis, growth, development, differentiation, apoptosis, and regulation of immunity (13)(14)(15)(16)(17)(18)(19)(20)(21)(22). Ets-2 plays an important role in the maturation, proliferation, and survival of mouse thymocytes, possibly by regulating the expression of c-Myc (23).…”

mentioning

confidence: 99%

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Transcription Factor Ets-2 Acts as a Preinduction Repressor of Interleukin-2 (IL-2) Transcription in Naive T Helper Lymphocytes

Panagoulias

Georgakopoulos

Αγγελετοπούλου

et al. 2016

Journal of Biological Chemistry

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Edited by Joel GottesfeldIL-2 is the first cytokine produced when naive T helper (Th) cells are activated and differentiate into dividing pre-Th0 proliferating precursors. IL-2 expression is blocked in naive, but not activated or memory, Th cells by the transcription factor Ets-2 that binds to the antigen receptor response element (ARRE)-2 of the proximal IL-2 promoter. Ets-2 acts as an independent preinduction repressor in naive Th cells and does not interact physically with the transcription factor NFAT (nuclear factor of activated T-cells) that binds to the ARRE-2 in activated Th cells. In naive Th cells, Ets-2 mRNA expression, Ets-2 protein levels, and Ets-2 binding to ARRE-2 decrease upon cell activation followed by the concomitant expression of IL-2. Cyclosporine A stabilizes Ets-2 mRNA and protein when the cells are activated. Ets-2 silences directly constitutive or induced IL-2 expression through the ARRE-2. Conversely, Ets-2 silencing allows for constitutive IL-2 expression in unstimulated cells. Ets-2 binding to ARRE-2 in chromatin is stronger in naive compared with activated or memory Th cells; in the latter, Ets-2 participates in a change of the IL-2 promoter architecture, possibly to facilitate a quick response when the cells re-encounter antigen. We propose that Ets-2 expression and protein binding to the ARRE-2 of the IL-2 promoter are part of a strictly regulated process that results in a physiological transition of naive Th cells to Th0 cells upon antigenic stimulation. Malfunction of such a repression mechanism at the molecular level could lead to a disturbance of later events in Th cell plasticity, leading to autoimmune diseases or other pathological conditions.

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Section: Discussionsupporting

confidence: 85%

mentioning

confidence: 99%

Transcription Factor Ets-2 Acts as a Preinduction Repressor of Interleukin-2 (IL-2) Transcription in Naive T Helper Lymphocytes

Panagoulias

Georgakopoulos

Αγγελετοπούλου

et al. 2016

Journal of Biological Chemistry

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“…The region contains 2 ETS transcription factors, ETS1 and FLI1. Known to be involved in the pathogenesis of multiple human cancers, 12,13 both ETS1 and FLI1 have an important role in the development of lymphoid tissues and immune system control, [14][15][16] regulating the activity of important players in B-cell growth and maturation such as the B-cell-specific activator protein PAX5 17,18 and the master regulator of plasma cell differentiation, PRDM1. 19 Notably, Ets1 and Fli1 are repressed during the late phases of B-cell differentiation in an in vitro murine system.…”

Section: Introductionmentioning

confidence: 99%

Deregulation of ETS1 and FLI1 contributes to the pathogenesis of diffuse large B-cell lymphoma

Bonetti

Testoni

Scandurra

et al. 2013

Blood

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Key Points• A recurrent gain of a region of chromosome 11 (11q24.3) occurs in up to one-quarter of cases of diffuse large B-cell lymphoma.• ETS1 and FLI1 genes are overexpressed and determine proliferation, survival, and differentiation arrest of the lymphoma cells.Diffuse large B-cell lymphoma (DLBCL) is the most common form of human lymphoma. DLBCL is a heterogeneous disease characterized by different genetic lesions. We herein report the functional characterization of a recurrent gain mapping on chromosome 11q24.3, found in 23% of 166 DLBCL cases analyzed. The transcription factors ETS1 and FLI1, located within the 11q24.3 region, had significantly higher expression in clinical samples carrying the gain. Functional studies on cell lines showed that ETS1 and FLI1 cooperate in sustaining DLBCL proliferation and viability and regulate genes involved in germinal center differentiation. Taken together, these data identify the 11q24.3 gain as a recurrent lesion in DLBCL leading to ETS1 and FLI1 deregulated expression, which can contribute to the pathogenesis of this disease. (Blood. 2013;122(13):2233-2241) IntroductionDiffuse large B-cell lymphoma (DLBCL) is the most common type of non-Hodgkin lymphoma, accounting for 25% to 30% of adult cases in western countries, and it is characterized by heterogeneous histopathological, biological, and clinical features.1 DLBCL has been molecularly classified in at least 3 subtypes, reflecting different stages of B-cell differentiation: germinal center B-cell-like DLBCL (GCB) from germinal center (GC) centroblasts, activated B-cell-like DLBCL (ABC) from GC cells undergoing plasmacytic differentiation, and an intermediate type 3 DLBCL. 2 Physiological GC B-cell differentiation requires a complex transcriptional program and DLBCL displays recurrent genetic abnormalities that typically circumvent this normal genetic program, allowing the neoplastic B cells to avoid plasmacytic differentiation and evade apoptosis.2 Briefly, chromosomal translocations involving the BCL2 oncogene and mutations of the EZH2 methyltransferase are almost exclusively observed in GCB DLBCL, 3 whereas ABC DLBCL are preferentially associated with a disruption of terminal B-cell differentiation program (ie, PRDM1 inactivation and BCL6 deregulation) 4,5 and constitutive activation of the nuclear factor kB (NF-kB) transcription pathway (most commonly via somatic mutations of TNFAIP3, CARD11, CD79B, and MYD88). [6][7][8] Other recurrent lesions can be found in all the DLBCL subtypes, including inactivation of histone and/or chromatin modifying genes CREBBP, EP300, and MLL2 9,10 and of genes involved in immune recognition, such as b2-microglobulin and CD58. 11 It is likely that additional, undescribed genetic defects may also contribute to the pathogenesis of DLBCL.In the present study, aimed to identify new recurrent genetic defects in DLBCL, we performed genomic profiling analysis on 166 DLBCL samples, which enabled us to characterize a new recurrent lesion on chromosome 11q24.3 occurring in up to onequarter of...

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“…As knowledge of the immune defenses in PCa remains incomplete, we recently reported the identification of immunity-related genes in PCa, and suggested (based on bioinformatical analysis) that the genes are potentially regulated by members of the ETS family of transcription factors (7), which are known to be involved in translocations frequently found in PCa (8), and are reported to be essential for the regulation of immunity-related genes (9). More specifically, our analysis revealed that 31 out of the 37 immunity-related genes that we have identified have potential binding sites for the ETS family prototype, ETS-1 (7).…”

Section: Discussionmentioning

confidence: 99%

“…Of note, our analysis of the promoter regions of the identified immunity-related genes revealed that 31 out of the 37 genes have potential binding sites for the ETS family prototype, ETS-1 (7). In the majority of PCa cases, recurrent gene fusions involving members of the ETS family have frequently been reported (8), along with reports suggesting that members of the family are essential for the regulation of the immune system and immunity-related genes (9).…”

Section: Introductionmentioning

confidence: 99%

Regulation of prostate cancer immunity-related genes in PC3 prostate cancer cells by ETS-1

Shaikhibrahim¹,

Lindstrot²,

Buettner³

et al. 2011

Oncology Letters

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Abstract. Prostate cancer (PCa) is one of the most prevalent forms of cancer affecting males worldwide, and knowledge of the immune defenses involved in PCa remains incomplete. Since the identification of immunity-related genes may have enormous implications for the understanding of PCa immunology, we recently reported the identification of immunity-related genes in PCa tissues and found potential binding sites for the ETS family prototype, ETS-1, in the majority of genes identified. Therefore, as a continuation of our previous study, we investigated whether ETS-1 regulates these genes in an in vitro PCa cell line model, PC3 cells. We specifically blocked ETS-1 in PC3 cells by transfection with an ETS-1 inverse antisense expression vector or a mock control vector. We then assessed the effect of the blockade on the expression of the recently identified PCa immunity-related genes using a comprehensive oligo gene expression microarray analysis. The results showed that ETS-1 is involved in the activation or repression of the recently identified immunity-related genes in PCa. These findings provide insights into the regulation of immunity-related genes in PCa, and emphasize the importance of ETS-1 in prostate cancer immunology.

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ETS transcription factors and regulation of immunity

Cited by 153 publications

References 195 publications

Transcription Factor Ets-2 Acts as a Preinduction Repressor of Interleukin-2 (IL-2) Transcription in Naive T Helper Lymphocytes

Transcription Factor Ets-2 Acts as a Preinduction Repressor of Interleukin-2 (IL-2) Transcription in Naive T Helper Lymphocytes

Deregulation of ETS1 and FLI1 contributes to the pathogenesis of diffuse large B-cell lymphoma

Regulation of prostate cancer immunity-related genes in PC3 prostate cancer cells by ETS-1

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