Ets and retroviruses–transduction and activation of members of the Ets oncogene family in viral oncogenesis

Blair, Donald G.; Athanasiou, Meropi

doi:10.1038/sj.onc.1204046

Cited by 31 publications

(27 citation statements)

References 84 publications

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“…A strong candidate is bcl-2, which is up-regulated by Myb-Ets in myeloid cells and by c-Myb in T cells, probably by direct interaction with its promoter. 47,48 Hox genes are another group of candidate target genes because these are often deregulated in human leukemias. 49,50 In particular, Hox11, which is associated with oncogenesis in human beings and mice, 51 transforms murine fetal liver cells with a phenotype similar to E26 transformants (K.M.M., unpublished observations 2001).…”

Section: Discussionmentioning

confidence: 99%

E26 leukemia virus converts primitive erythroid cells into cycling multilineage progenitors

McNagny

Graf

2003

Blood

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Acute chicken leukemia retroviruses, because of their capacity to readily transform hematopoietic cells in vitro, are ideal models to study the mechanisms governing the cell-type specificity of oncoproteins. Here we analyzed the transformation specificity of 2 acute chicken leukemia retroviruses, the Myb-Etsencoding E26 virus and the ErbA/ErbBencoding avian erythroblastosis virus IntroductionThe first leukemia-inducing oncogenes discovered are those transduced by acute avian leukemia viruses. These genes encode truncated or mutated forms of cellular proteins. Acute leukemia viruses are relatively common in chickens, probably reflecting this species' unusual susceptibility to the transforming effects of a variety of oncoproteins. More than 10 different isolates of acute avian leukemia viruses have been identified, each inducing a distinct type of leukemia within a matter of weeks in vivo and transforming cultured hematopoietic cells within a few days of infection. 1 Cells transformed in vivo and in vitro closely resemble each other. 2,3 Thus, for example, hematopoietic cells transformed by the Myb-encoding avian myeloblastosis virus (AMV) resemble monoblasts while cells transformed by the ErbB and ErbA proteins of the avian erythroblastosis virus (AEV) resemble erythroblasts both in the animal and in tissue culture. [4][5][6] Crude fractionation experiments using adherence and cytotoxic antibodies as selection methods suggested that these viruses block the differentiation of their respective target cells. 7 Additional experiments have shown that transformation specificity is a property mediated by the individual viral oncogene(s) and not by the specificity of the viral envelope. 8 An exception to the rule is the avian acute leukemia E26 virus, which encodes a fused oncoprotein between the truncated cellular transcriptional activators c-Myb and c-Ets-1. This virus was originally described as an erythroleukemia virus, based on the expression in leukemic cells of the erythroid-specific histone H5 and the observation that E26-transformed hematopoietic colonies contained a small number of mature erythroid cells. 9 In addition, myelomonocytic precursors ("myeloblasts") were seen within the leukemic cell population of infected animals, and this cell type could be transformed in culture as well. 2,3 The virus therefore transforms 2 different cell types and induces a mixed "erythroid"/ myeloid leukemia. Subsequent studies have shown that the transformed "erythroid" cells actually resemble thromboblasts (the avian equivalents of megakaryocytes, which give rise to thrombocytes) and that they are, in fact, multipotent. Thus, they can be induced to differentiate into erythrocytes and thrombocytes by inactivation of the viral Ets and Myb proteins, respectively, 10,11 and into eosinophils and myeloblasts (granulocyte/macrophage precursors 12 ) by activation of the Ras and protein kinase C (PKC) pathways. 12,13 In addition, E26-transformed cells (called MEPs for Myb-Ets-transformed progenitors) express cell surface antigens cha...

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Section: Discussionmentioning

confidence: 99%

E26 leukemia virus converts primitive erythroid cells into cycling multilineage progenitors

McNagny

Graf

2003

Blood

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“…One such transcriptional regulator is FLI-1, another member of the ETS family of transcription factors. FLI-1 induces erythroleukemia in newborn mice (as a result of infection by a component of the Friend virus) as opposed to in adult mice in the case of PU.1 (Blair and Athanasiou, 2000). Nevertheless, expression of these transcriptional regulators alone is not sufficient to produce erythroleukemia in mice.…”

Section: Transformation Of Human Erythroid Cellsmentioning

confidence: 99%

“…PU.1 belongs to the E26 transformation specific (ETS) family of transcription factors, which are also known to play a role in avian erythroleukemia (Blair and Athanasiou, 2000). On the basis of a large number of studies on the role of PU.1, it is well established that in order for erythroid progenitors to continue their normal differentiation program PU.1 expression must be switched off very early at the time of commitment of the erythroid lineage.…”

Section: Transformation Of Human Erythroid Cellsmentioning

confidence: 99%

“…The Friend virus has two variants, the spleen focus-forming virus (SFFV) polycythemia strain (SFFV-P) and SFFV anemia strain (SFFV-A). The pathogenicity of SFFV is due to the envelope protein gp55, which binds the erythropoietin (Epo) receptor and activates it in the absence of Epo (Blair and Athanasiou, 2000;Ney and D'Andrea, 2000). Both SFFV polycythemia and SFFV anemia strains cause disease in the erythroid lineage although they act quite differently.…”

Section: Transformation Of Human Erythroid Cellsmentioning

confidence: 99%

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Erythroid and megakaryocytic transformation

Wickrema

Crispino

2007

Oncogene

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Red blood cells and megakaryocytes arise from a common precursor, the megakaryocyte-erythroid progenitor and share many regulators including the transcription factors GATA-1 and GFI-1B and signaling molecules such as JAK2 and STAT5. These lineages also share the distinction of being associated with rare, but aggressive malignancies that have very poor prognoses. In this review, we will briefly summarize features of normal development of red blood cells and megakaryocytes and also highlight events that lead to their leukemic transformation. It is clear that much more work needs to be done to improve our understanding of the unique biology of these leukemias and to pave the way for novel targeted therapeutics.

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“…The established molecular pathophysiology associated with some of these mechanisms are listed. The literature on ETS proteins is vast and this summary is only intended to be illustrative; readers interested in specific aspects or paralogs mentioned in this figure are referred to reviews and studies such as the following: 26,49,51,53,66,[87][88][89][90][91][92][93] Note that auto-inhibition (indicated by the cartoon helix) is not a universal feature of ETS proteins; several paralogs, such as PU.1, are not auto-inhibited. Abbreviations: AML, acute myeloid leukemia; Ca, cancer; cHD, classical Hodgkin's disease; MM, multiple myeloma.…”

Section: Role Of Molecular Hydration In Dna Recognition By Ets Proteinsmentioning

confidence: 99%

Signatures of DNA target selectivity by ETS transcription factors

Poon

Kim

2017

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The ETS family of transcription factors is a functionally heterogeneous group of gene regulators that share a structurally conserved, eponymous DNA-binding domain. DNA target specificity derives from combinatorial interactions with other proteins as well as intrinsic heterogeneity among ETS domains. Emerging evidence suggests molecular hydration as a fundamental feature that defines the intrinsic heterogeneity in DNA target selection and susceptibility to epigenetic DNA modification. This perspective invokes novel hypotheses in the regulation of ETS proteins in physiologic osmotic stress, their pioneering potential in heterochromatin, and the effects of passive and pharmacologic DNA demethylation on ETS regulation.

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Ets and retroviruses–transduction and activation of members of the Ets oncogene family in viral oncogenesis

Cited by 31 publications

References 84 publications

E26 leukemia virus converts primitive erythroid cells into cycling multilineage progenitors

E26 leukemia virus converts primitive erythroid cells into cycling multilineage progenitors

Erythroid and megakaryocytic transformation

Signatures of DNA target selectivity by ETS transcription factors

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