Loss of MicroRNA Targets in the 3′ Untranslated Region as a Mechanism of Retroviral Insertional Activation of Growth Factor Independence 1

Dabrowska, Magdalena; Dybkær, Karen; Johnsen, Hans Erik; Bruce, Wang; Wabl, Matthias; Pedersen, Finn Skou

doi:10.1128/jvi.00427-09

Cited by 24 publications

(18 citation statements)

References 83 publications

(97 reference statements)

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“…15,17,21 Gfi1 protein expression is also regulated by microRNAs. 22 Finally, Gfi1 expression is also regulated at the protein level through ubiquitin-proteasome-mediated degradation. 23,24 Expression of Gfi1 and Gfi1b is therefore tightly regulated at multiple levels.…”

Section: Structure and Expression Regulation Of Gfi1 And Gfi1b Proteinsmentioning

confidence: 99%

Gfi1 and Gfi1b: key regulators of hematopoiesis

2010

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Transcription factor Growth factor independence 1 (Gfi1) is required for multilineage blood cell development, from stem and progenitor cells to differentiated lymphoid and myeloid cells. Gfi1 expression is rapidly induced by cytokines that control both the adaptive and innate immune systems. Gfi1 itself represses the expression of genes implicated in cell survival, proliferation and differentiation. Changes in Gfi1 expression and function have not only been implicated in neutropenia, allergy, autoimmunity and hyperinflammatory responses, but also in lymphoma and more recently in the development of leukemia. In this study, we review how Gfi1 and its paralogue Gfi1b control the development of blood cells, discuss how changes in Gfi1 and Gfi1b function contribute to hematological disease and report on the molecular function of these proteins.

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Section: Structure and Expression Regulation Of Gfi1 And Gfi1b Proteinsmentioning

confidence: 99%

Gfi1 and Gfi1b: key regulators of hematopoiesis

2010

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“…Sh2d1a , Cask , Mr1 , and Stx6 showed the highest upregulation in the tumors where they were found as integrations, indicating an activating effect of the integrated retrovirus on these genes. The expression of Notch1 , Myc , Rasgrp1 , Rras2 and the D-type cyclines, which are major common integration target in many MLV induced lymphomas [20,22,28,30], remained unchanged in both overall gene expression and in the individual tumors where they were found as integrations. Although our results indicate that the presence of a virus in the vicinity of a gene does not always alter its expression, we cannot exclude whether or not there is an oncogenic effect of the integrations on protein stability or alternative splicing, as we only analyzed the summarized gene expression.…”

Section: Discussionmentioning

confidence: 99%

Gene expression profiling of murine T-cell lymphoblastic lymphoma identifies deregulation of S-phase initiating genes

et al. 2013

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In a search for genes and pathways implicated in T-cell lymphoblastic lymphoma (T-LBL) development, we used a murine lymphoma model, where mice of the NMRI-inbred strain were inoculated with murine leukemia virus mutants. The resulting tumors were analyzed by integration analysis and global gene expression profiling to determine the effect of the retroviral integrations on the nearby genes, and the deregulated pathways in the tumors. Gene expression profiling identified increased expression of genes involved in the minichromosome maintenance and origin of recognition pathway as well as downregulation in negative regulators of G1/S transition, indicating increased S-phase initiation in murine T-LBLs.

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“…Dabrowska et al demonstrated how MMLV insertion mutagenesis overcomes miR targeting to activate Gfi1 expression [69]. While insertion sites in the Gfi1 3′ UTR were known to lead to increased transcript levels [2,70], these insertions also truncate the Gfi1 transcript to eliminate binding sites for a number of miRs, including miR-155 and miR-10a [69].…”

Section: Gfi1 In Lymphoid Leukemiamentioning

confidence: 99%

Gfi1–cells and circuits: unraveling transcriptional networks of development and disease

Phelan¹,

Shroyer²,

Cook³

et al. 2010

Current Opinion in Hematology

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Purpose of review-The review will integrate current knowledge of transcriptional circuits whose dysregulation leads to autoimmunity, neutropenia and leukemia.Recent findings-Growth factor independent-1 is a transcriptional repressor with essential roles in controlling hematopoietic stem cell biology, myeloid and lymphoid differentiation and lymphocyte effector functions. Recent work has suggested that Gfi1 competes or collaborates with other transcription factors to modulate transcription programs and lineage decisions.Summary-Gfi1 is central to several transcriptional circuits whose dysregulation leads to abnormal or malignant hematopoiesis. These functional relationships are conserved from Drosophila development. Such conserved pathways represent central oncogenic or "gatekeeper" pathways that are pivotal to understanding the process of cellular transformation, and illustrate key targets for clinical intervention.

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Loss of MicroRNA Targets in the 3′ Untranslated Region as a Mechanism of Retroviral Insertional Activation of Growth Factor Independence 1

Cited by 24 publications

References 83 publications

Gfi1 and Gfi1b: key regulators of hematopoiesis

Gfi1 and Gfi1b: key regulators of hematopoiesis

Gene expression profiling of murine T-cell lymphoblastic lymphoma identifies deregulation of S-phase initiating genes

Gfi1–cells and circuits: unraveling transcriptional networks of development and disease

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